Variant rs7082289 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_052918.5(SORCS1):c.3069G>A(p.Ala1023=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,766 control chromosomes in the GnomAD database, including 14,820 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2590 hom., cov: 32)

Exomes 𝑓: 0.11 ( 12230 hom. )

Consequence

SORCS1
NM_052918.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Variant links:

Genes affected

SORCS1 (HGNC:16697): (sortilin related VPS10 domain containing receptor 1) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. Two of the five family members (sortilin and sortilin-related receptor) are synthesized as preproproteins; it is not yet known if this encoded protein is also a preproprotein. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

SORCS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP7

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5 linkuse as main transcript	c.3069G>A	p.Ala1023=	synonymous_variant	23/26	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11 linkuse as main transcript	c.3069G>A	p.Ala1023=	synonymous_variant	23/26	1	NM_052918.5	ENSP00000263054	P1	Q8WY21-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23765

AN:

151958

Hom.:

2590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0828

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.0991

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0870

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.140

AC:

34977

AN:

250572

Hom.:

3552

AF XY:

0.146

AC XY:

19771

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.0840

Gnomad ASJ exome

AF:

0.0840

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.0850

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.109

AC:

158690

AN:

1461690

Hom.:

12230

Cov.:

AF XY:

0.114

AC XY:

83191

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.0849

Gnomad4 ASJ exome

AF:

0.0844

Gnomad4 EAS exome

AF:

0.219

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0838

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.156

AC:

23773

AN:

152076

Hom.:

2590

Cov.:

AF XY:

0.159

AC XY:

11850

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.283

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.0828

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.331

Gnomad4 FIN

AF:

0.0991

Gnomad4 NFE

AF:

0.0870

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.109

Hom.:

910

Bravo

AF:

0.157

Asia WGS

AF:

0.286

AC:

993

AN:

3478

EpiCase

AF:

0.0904

EpiControl

AF:

0.0869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.027

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over