VCV000191289.29 - ClinVar

NM_000326.5(RLBP1):c.286_297del (p.Phe96_Phe99del)

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.

(8)

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.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000326.5(RLBP1):c.286_297del (p.Phe96_Phe99del)

Variation ID: 191289 Accession: VCV000191289.29

Type and length

Deletion, 12 bp

Location

Cytogenetic: 15q26.1 15: 89217169-89217180 (GRCh38) [ NCBI UCSC ] 15: 89760400-89760411 (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	Jun 2, 2015	Feb 14, 2024	Jan 10, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000326.5:c.286_297del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000317.1:p.Phe96_Phe99del	inframe deletion
NM_000326.5:c.286_297delTTCCTGCGCTTC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000326.4:c.286_297del
NC_000015.10:g.89217174_89217185del
NC_000015.9:g.89760405_89760416del
NG_008116.1:g.9512_9523del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000015.10:89217168:GAAGCGCAGGAAGAAGC:GAAGC

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.

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

Links

ClinGen: CA210020 dbSNP: rs786205626 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.
RLBP1		-	-	GRCh38 GRCh37	387	428

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 provided	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jan 10, 2024	RCV000171480.7
Bothnia retinal dystrophy	Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jan 3, 2022	RCV000197318.2
Retinitis punctata albescens	Pathogenic (1)	no assertion criteria provided	Jun 23, 2019	RCV001003176.1
Retinal dystrophy	Likely pathogenic (1)	criteria provided, single submitter	Jul 16, 2018	RCV001075081.2
Autosomal recessive retinitis pigmentosa	Pathogenic (1)	no assertion criteria provided	Sep 10, 2015	RCV001257813.1
Abnormality of the eye	Likely pathogenic (1)	criteria provided, single submitter	Jul 10, 2021	RCV001814088.1

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.
Likely pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Not provided Affected status: yes Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV000221679.1 First in ClinVar: Jun 02, 2015 Last updated: Jun 02, 2015	Indication for testing: Vision phenotype
Likely pathogenic (Jul 16, 2018)	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme) Method: clinical testing	Retinal dystrophy Affected status: yes Allele origin: germline	Blueprint Genetics Accession: SCV001240692.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 Comment: My Retina Tracker patient
Pathogenic (Jan 10, 2024)	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: SCV002237180.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024	Publications: PubMed (3) PubMed: 25326637‚ 26355662‚ 32188692 Comment: This variant, c.286_297del, results in the deletion of 4 amino acid(s) of the RLBP1 protein (p.Phe96_Phe99del), but otherwise preserves the integrity of the reading frame. … (more) This variant, c.286_297del, results in the deletion of 4 amino acid(s) of the RLBP1 protein (p.Phe96_Phe99del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs786205626, gnomAD 0.0009%). This variant has been observed in individual(s) with clinical features of retinitis punctata albescens (PMID: 25326637, 26355662, 32188692). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 191289). For these reasons, this variant has been classified as Pathogenic. (less)
Likely pathogenic (Feb 04, 2014)	criteria provided, single submitter (Lee et al. (JAMA. 2014)) Method: clinical testing	Bothnia retinal dystrophy (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	UCLA Clinical Genomics Center, UCLA Study: CES Accession: SCV000255448.2 First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015	Age: 50-59 years Sex: male Ethnicity/Population group: Palestinian Testing laboratory: UCLA Clinical Genomics Center
Likely pathogenic (Jan 03, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Bothnia retinal dystrophy Affected status: yes Allele origin: germline	3billion Accession: SCV002058155.1 First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022	Publications: PMID:26355662 PMID:26355662 Comment: This inframe deletion in the non-repeat region can change the length of the protein and disrupt protein function (PM4_M). The variant has been reported at … (more) This inframe deletion in the non-repeat region can change the length of the protein and disrupt protein function (PM4_M). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000191289, PMID:26355662, 3billion dataset).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. (less) Clinical Features: Visual impairment (present) , Abnormal retinal morphology (present)
Likely pathogenic (Jul 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Abnormality of the eye Affected status: yes Allele origin: germline	Kariminejad - Najmabadi Pathology & Genetics Center Accession: SCV001755498.1 First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022
Pathogenic (Sep 10, 2015)	no assertion criteria provided Method: literature only	Autosomal recessive Retinitis Pigmentosa Affected status: yes Allele origin: germline	Faculty of Health Sciences, Beirut Arab University Accession: SCV001434597.1 First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020	Publications: PubMed (1) PubMed: 26355662 Number of individuals with the variant: 1 Ethnicity/Population group: Arab
Pathogenic (Jun 23, 2019)	no assertion criteria provided Method: research	Retinitis punctata albescens Affected status: yes Allele origin: inherited	Sharon lab, Hadassah-Hebrew University Medical Center Accession: SCV001161252.1 First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020

Comment:

This variant, c.286_297del, results in the deletion of 4 amino acid(s) of the RLBP1 protein (p.Phe96_Phe99del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs786205626, gnomAD 0.0009%). This variant has been observed in individual(s) with clinical features of retinitis punctata albescens (PMID: 25326637, 26355662, 32188692). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 191289). For these reasons, this variant has been classified as Pathogenic.

Comment:

This inframe deletion in the non-repeat region can change the length of the protein and disrupt protein function (PM4_M). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000191289, PMID:26355662, 3billion dataset).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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
Effects of deficiency in the RLBP1-encoded visual cycle protein CRALBP on visual dysfunction in humans and mice.	Lima de Carvalho JR Jr	The Journal of biological chemistry	2020	PMID: 32188692
Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies.	Patel N	Genetics in medicine : official journal of the American College of Medical Genetics	2016	PMID: 26355662
Clinical exome sequencing for genetic identification of rare Mendelian disorders.	Lee H	JAMA	2014	PMID: 25326637

Text-mined citations for rs786205626 ...

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 Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000326.5(RLBP1):c.286_297del (p.Phe96_Phe99del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs786205626 ...