rs10491051

Variant names:

• chr10-106634686-G-A
• rs10491051
• NM_052918.5:c.2476-5298C>T

Variant summary

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

The NM_052918.5(SORCS1):​c.2476-5298C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,982 control chromosomes in the GnomAD database, including 4,829 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 (4829 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.2476-5298C>T		intron_variant	Intron 18 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.2476-5298C>T		intron_variant	Intron 18 of 25	1	NM_052918.5	ENSP00000263054.5
SORCS1	ENST00000369698.6	c.1207-5298C>T		intron_variant	Intron 10 of 18	5		ENSP00000358712.2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34470 AN: 151862 Hom.: 4829 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.177

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: 0.227 AC: 34498 AN: 151982 Hom.: 4829 Cov.: 32 AF XY: 0.230 AC XY: 17090 AN XY: 74264

African (AFR) AF: 0.366 AC: 15147 AN: 41424

American (AMR) AF: 0.158 AC: 2418 AN: 15276

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

East Asian (EAS) AF: 0.517 AC: 2666 AN: 5160

South Asian (SAS) AF: 0.329 AC: 1589 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1574 AN: 10566

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10100 AN: 67954

Other (OTH) AF: 0.195 AC: 410 AN: 2100

Alfa AF: 0.183 Hom.: 382

Bravo AF: 0.234

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		0.18
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: rs10491051; hg19: chr10-108394444;