VCV000338569.17 - ClinVar

NM_001250.6(CD40):c.-1T>C

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(10)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001250.6(CD40):c.-1T>C

Variation ID: 338569 Accession: VCV000338569.17

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 20q13.12 20: 46118343 (GRCh38) [ NCBI UCSC ] 20: 44746982 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 6, 2016	Sep 29, 2024	Jan 24, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001250.6:c.-1T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		5 prime UTR
NM_001302753.2:c.-1T>C		5 prime UTR
NM_001322421.2:c.-1T>C		5 prime UTR
NM_001322422.2:c.-1T>C		5 prime UTR
NM_001362758.2:c.-1T>C		5 prime UTR
NM_152854.4:c.-1T>C		5 prime UTR
NR_126502.2:n.30T>C		non-coding transcript variant
NR_136327.2:n.30T>C		non-coding transcript variant
NC_000020.11:g.46118343T>C
NC_000020.10:g.44746982T>C
NG_007279.1:g.5077T>C
NG_143175.2:g.948T>C
LRG_40:g.5077T>C
LRG_40t1:c.-1T>C

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000020.11:46118342:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.22883 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.74785

Exome Aggregation Consortium (ExAC) 0.75273

1000 Genomes Project 0.77117

1000 Genomes Project 30x 0.77701

The Genome Aggregation Database (gnomAD) 0.79882

Trans-Omics for Precision Medicine (TOPMed) 0.80274

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.80301

Links

ClinGen: CA9888328 dbSNP: rs1883832 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CD40		-	-	GRCh38 GRCh37	237	272
LOC127893450	-	-	-	GRCh38	-	28

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (3)	criteria provided, multiple submitters, no conflicts	Jan 24, 2024	RCV000456068.7
Hyper-IgM syndrome type 3	Benign (4)	criteria provided, multiple submitters, no conflicts	Jul 14, 2021	RCV000608869.8
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Apr 9, 2023	RCV001691965.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Mar 28, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000538639.1 First in ClinVar: Apr 09, 2017 Last updated: Apr 09, 2017	Comment: Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more) Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less) Method: Genome/Exome Filtration
Benign (Jul 28, 2017)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Hyper-IgM syndrome type 3 Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV000743108.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Hyper-IgM syndrome type 3 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000434125.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jul 07, 2020)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001426777.1 First in ClinVar: Aug 09, 2020 Last updated: Aug 09, 2020	Publications: PubMed (8) PubMed: 18446002‚ 15307939‚ 15731360‚ 17344890‚ 14611700‚ 12593727‚ 15272925‚ 17949264
Benign (Jul 14, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hyper-IgM syndrome type 3 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001776177.1 First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 2021	Sex: mixed
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001915141.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Comment: This variant is associated with the following publications: (PMID: 20137882, 18287517, 20127135, 21091218, 17344890, 20473910, 23669336, 18097708, 20634952, 24828072, 15731360, 27745838, 29780830, 31373353, 31642196, 23954880)
Benign (Jan 24, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan Accession: SCV004232908.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024	Comment: This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied by a panel of primary … (more) This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 90. Only high quality variants are reported. (less) Number of individuals with the variant: 90 Age: <18 years Sex: mixed
Benign (Apr 09, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003443374.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005313932.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (-)	no assertion criteria provided Method: clinical testing	Hyper-IgM syndrome type 3 Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000734077.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018

Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A C/T polymorphism in CD40 gene is not associated with susceptibility and phenotype of Graves' disease in Taiwanese.	Hsiao JY	Endocrine journal	2008	PMID: 18446002
Susceptible alleles of the CD40 and CTLA-4 genes are not associated with the relapse after antithyroid withdrawal in Graves' disease.	Kim KW	Thyroid : official journal of the American Thyroid Association	2007	PMID: 17949264
A CD40 Kozak sequence polymorphism and susceptibility to antibody-mediated autoimmune conditions: the role of CD40 tissue-specific expression.	Jacobson EM	Genes and immunity	2007	PMID: 17344890
A Graves' disease-associated Kozak sequence single-nucleotide polymorphism enhances the efficiency of CD40 gene translation: a case for translational pathophysiology.	Jacobson EM	Endocrinology	2005	PMID: 15731360
Role of the CD40 locus in Graves' disease.	Houston FA	Thyroid : official journal of the American Thyroid Association	2004	PMID: 15307939
A single nucleotide polymorphism in the CD40 gene on chromosome 20q (GD-2) provides no evidence for susceptibility to Graves' disease in UK Caucasians.	Heward JM	Clinical endocrinology	2004	PMID: 15272925
A C/T polymorphism in the 5'-untranslated region of the CD40 gene is associated with Graves' disease in Koreans.	Kim TY	Thyroid : official journal of the American Thyroid Association	2003	PMID: 14611700
A C/T single-nucleotide polymorphism in the region of the CD40 gene is associated with Graves' disease.	Tomer Y	Thyroid : official journal of the American Thyroid Association	2002	PMID: 12593727

Text-mined citations for rs1883832 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001250.6(CD40):c.-1T>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1883832 ...