rs10884387

Variant names:

• chr10-106932394-C-T
• rs10884387
• NM_052918.5:c.626+24119G>A

Variant summary

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

The NM_052918.5(SORCS1):​c.626+24119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,952 control chromosomes in the GnomAD database, including 6,579 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 0.28 (6579 hom., cov: 31)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 8 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.626+24119G>A		intron_variant	Intron 2 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.626+24119G>A		intron_variant	Intron 2 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43128 AN: 151832 Hom.: 6582 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.284 AC: 43127 AN: 151952 Hom.: 6579 Cov.: 31 AF XY: 0.282 AC XY: 20943 AN XY: 74278

African (AFR) AF: 0.181 AC: 7505 AN: 41440

American (AMR) AF: 0.280 AC: 4271 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3466

East Asian (EAS) AF: 0.169 AC: 873 AN: 5172

South Asian (SAS) AF: 0.265 AC: 1273 AN: 4806

European-Finnish (FIN) AF: 0.298 AC: 3147 AN: 10552

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23891 AN: 67936

Other (OTH) AF: 0.296 AC: 624 AN: 2106

Alfa AF: 0.326 Hom.: 14346

Bravo AF: 0.273

Asia WGS AF: 0.216 AC: 752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		-0.047
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: rs10884387; hg19: chr10-108692152;