rs10786981

chr10-106921972-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052918.5(SORCS1):c.626+34541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,128 control chromosomes in the GnomAD database, including 22,466 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 0.52 (22466 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS1	NM_052918.5	c.626+34541T>C		intron_variant		ENST00000263054.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS1	ENST00000263054.11	c.626+34541T>C		intron_variant		1	NM_052918.5	P1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79629 AN: 152010 Hom.: 22456 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.524 AC: 79681 AN: 152128 Hom.: 22466 Cov.: 32 AF XY: 0.523 AC XY: 38918 AN XY: 74396

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.551

Alfa AF: 0.590 Hom.: 7149

Bravo AF: 0.508

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.030
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10786981; hg19: chr10-108681730;