chr10-106634856-C-A

Variant names:

• chr10-106634856-C-A
• rs10491052
• NM_052918.5:c.2476-5468G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387556.1(SORCS1):​c.2476-5468G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,110 control chromosomes in the GnomAD database, including 4,808 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 0.23 (4808 hom., cov: 33)
• Consequence: SORCS1 NM_001387556.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 4 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387556.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	NM_052918.5	MANE Select	c.2476-5468G>T		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.2476-5468G>T		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.2476-5468G>T		intron	N/A	NP_001013049.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.2476-5468G>T		intron	N/A	ENSP00000263054.5
	SORCS1	ENST00000369698.6	TSL:5	c.1207-5468G>T		intron	N/A	ENSP00000358712.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34410 AN: 151990 Hom.: 4808 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34435 AN: 152110 Hom.: 4808 Cov.: 33 AF XY: 0.230 AC XY: 17069 AN XY: 74362

African (AFR) AF: 0.364 AC: 15083 AN: 41476

American (AMR) AF: 0.158 AC: 2411 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3470

East Asian (EAS) AF: 0.516 AC: 2667 AN: 5166

South Asian (SAS) AF: 0.329 AC: 1588 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1575 AN: 10588

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10105 AN: 67988

Other (OTH) AF: 0.196 AC: 413 AN: 2112

Alfa AF: 0.175 Hom.: 8695

Bravo AF: 0.234

Asia WGS AF: 0.405 AC: 1406 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		0.074
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10491052; hg19: chr10-108394614;