NM_004176.5(SREBF1):c.1579C>T (p.Arg527Cys) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 8, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001586039.9

Allele description [Variation Report for NM_004176.5(SREBF1):c.1579C>T (p.Arg527Cys)]

NM_004176.5(SREBF1):c.1579C>T (p.Arg527Cys)

Gene:

SREBF1:sterol regulatory element binding transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_004176.5(SREBF1):c.1579C>T (p.Arg527Cys)

HGVS:

NC_000017.11:g.17817283G>A
NG_029029.1:g.24729C>T
NM_001005291.3:c.1669C>T
NM_001321096.3:c.1507C>T
NM_001388385.1:c.1579C>T
NM_001388386.1:c.1579C>T
NM_001388387.1:c.1618C>T
NM_001388388.1:c.1534C>T
NM_001388389.1:c.1573C>T
NM_001388390.1:c.1561C>T
NM_001388391.1:c.1552C>T
NM_001388392.1:c.1357C>T
NM_001388393.1:c.1404+413C>T
NM_001388394.1:c.1147C>T
NM_004176.5:c.1579C>TMANE SELECT
NP_001005291.1:p.Arg557Cys
NP_001308025.1:p.Arg503Cys
NP_001375314.1:p.Arg527Cys
NP_001375315.1:p.Arg527Cys
NP_001375316.1:p.Arg540Cys
NP_001375317.1:p.Arg512Cys
NP_001375318.1:p.Arg525Cys
NP_001375319.1:p.Arg521Cys
NP_001375320.1:p.Arg518Cys
NP_001375321.1:p.Arg453Cys
NP_001375323.1:p.Arg383Cys
NP_004167.3:p.Arg527Cys
NP_004167.3:p.Arg527Cys
NC_000017.10:g.17720597G>A
NM_001005291.2:c.1669C>T
NM_004176.3:c.1579C>T
NM_004176.4:c.1579C>T
NR_170943.1:n.1748C>T
NR_170944.1:n.1748C>T
NR_170945.1:n.1838C>T
NR_170990.1:n.1748C>T

Protein change:

R383C; ARG527CYS

Links:

OMIM: 184756.0001; OMIM: 184756.0004; dbSNP: rs2033690347

NCBI 1000 Genomes Browser:

rs2033690347

Molecular consequence:

NM_001388393.1:c.1404+413C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001005291.3:c.1669C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321096.3:c.1507C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388385.1:c.1579C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388386.1:c.1579C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388387.1:c.1618C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388388.1:c.1534C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388389.1:c.1573C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388390.1:c.1561C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388391.1:c.1552C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388392.1:c.1357C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001388394.1:c.1147C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004176.5:c.1579C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_170943.1:n.1748C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_170944.1:n.1748C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_170945.1:n.1838C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_170990.1:n.1748C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001810943	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 8, 2022)	germline	clinical testing	Citation Link,
SCV002568858	Laboratoire de Génétique Moléculaire, CHU Bordeaux	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001810943

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 8, 2022)

germline

clinical testing

Citation Link,

SCV002568858

Laboratoire de Génétique Moléculaire, CHU Bordeaux

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV001810943.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate a damaging effect (impairment of S1P cleavage and prohibition of nuclear translocation of the transciptionally active form of SREBP1) (Wang et al., 2020); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32902915, 33253727, 31790666, 32497488)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratoire de Génétique Moléculaire, CHU Bordeaux, SCV002568858.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

ClinVar

Relating variation to medicine