rs7082289

chr10-106607262-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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]

ACMG classification

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	UniProt
SORCS1	NM_052918.5	c.3069G>A	p.Ala1023=	synonymous_variant	23/26	ENST00000263054.11

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23765 AN: 151958 Hom.: 2590 Cov.: 32

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

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.: 32 AF XY: 0.114 AC XY: 83191 AN XY: 727140

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.: 32 AF XY: 0.159 AC XY: 11850 AN XY: 74330

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

Other links and lift over

dbSNP: rs7082289; hg19: chr10-108367020; COSMIC: COSV53862637; COSMIC: COSV53862637;