dbSNP rs7082289: SORCS1:p.Ala1023Ala (chr10-106607262-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_052918.5(SORCS1):c.3069G>A(p.Ala1023Ala) 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

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

SORCS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.109).

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 rank	MANE	Protein	UniProt
SORCS1	NM_052918.5 link	c.3069G>A	p.Ala1023Ala	synonymous_variant	Exon 23 of 26	ENST00000263054.11	NP_443150.3	Q8WY21-1B3KWN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11 link	c.3069G>A	p.Ala1023Ala	synonymous_variant	Exon 23 of 26	1	NM_052918.5	ENSP00000263054.5		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

GnomAD2 exomes

AF:

0.140

AC:

34977

AN:

250572

AF XY:

0.146

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 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

African (AFR)

AF:

0.293

AC:

9808

AN:

33472

American (AMR)

AF:

0.0849

AC:

3796

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0844

AC:

2206

AN:

26136

East Asian (EAS)

AF:

0.219

AC:

8703

AN:

39672

South Asian (SAS)

AF:

0.317

AC:

27358

AN:

86240

European-Finnish (FIN)

AF:

0.101

AC:

5383

AN:

53380

Middle Eastern (MID)

AF:

0.126

AC:

726

AN:

5768

European-Non Finnish (NFE)

AF:

0.0838

AC:

93151

AN:

1111922

Other (OTH)

AF:

0.125

AC:

7559

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

7536

15073

22609

30146

37682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.156

AC:

23773

AN:

152076

Hom.:

2590

Cov.:

AF XY:

0.159

AC XY:

11850

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.283

AC:

11730

AN:

41466

American (AMR)

AF:

0.106

AC:

1618

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0828

AC:

287

AN:

3466

East Asian (EAS)

AF:

0.238

AC:

1220

AN:

5130

South Asian (SAS)

AF:

0.331

AC:

1596

AN:

4824

European-Finnish (FIN)

AF:

0.0991

AC:

1050

AN:

10596

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0870

AC:

5913

AN:

67982

Other (OTH)

AF:

0.143

AC:

301

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

978

1956

2935

3913

4891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.109

Hom.:

1156

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

(source)

DANN

Benign

0.42

PhyloP100

-2.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs7082289

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over