rs2486152

Variant names:

• chr10-106738320-A-G
• rs2486152
• NM_052918.5:c.960-8206T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-106738320-A-G
• chr10-106738320-A-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.960-8206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,202 control chromosomes in the GnomAD database, including 49,671 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 0.80 (49671 hom., cov: 34)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.960-8206T>C		intron_variant	Intron 5 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.960-8206T>C		intron_variant	Intron 5 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122290 AN: 152084 Hom.: 49633 Cov.: 34

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.804 AC: 122388 AN: 152202 Hom.: 49671 Cov.: 34 AF XY: 0.799 AC XY: 59446 AN XY: 74396

African (AFR) AF: 0.715 AC: 29691 AN: 41512

American (AMR) AF: 0.839 AC: 12821 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2939 AN: 3472

East Asian (EAS) AF: 0.532 AC: 2749 AN: 5164

South Asian (SAS) AF: 0.724 AC: 3498 AN: 4830

European-Finnish (FIN) AF: 0.833 AC: 8826 AN: 10590

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59070 AN: 68022

Other (OTH) AF: 0.815 AC: 1725 AN: 2116

Alfa AF: 0.831 Hom.: 6823

Bravo AF: 0.801

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.70
PhyloP100		-1.8
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: rs2486152; hg19: chr10-108498078;