rs821942

chr10-106683087-C-Gchr10-106683087-C-T

Variant summary

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

The NM_052918.5(SORCS1):c.1561-3353G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,142 control chromosomes in the GnomAD database, including 54,172 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 0.83 (54172 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS1	NM_052918.5	c.1561-3353G>C		intron_variant		ENST00000263054.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS1	ENST00000263054.11	c.1561-3353G>C		intron_variant		1	NM_052918.5	P1
SORCS1	ENST00000369698.6	c.293-3353G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126856 AN: 152024 Hom.: 54157 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.834 AC: 126923 AN: 152142 Hom.: 54172 Cov.: 32 AF XY: 0.832 AC XY: 61865 AN XY: 74372

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.857

Alfa AF: 0.878 Hom.: 3053

Bravo AF: 0.820

Asia WGS AF: 0.700 AC: 2434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.8
Dann	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs821942; hg19: chr10-108442845;