rs10491052

chr10-106634856-C-Achr10-106634856-C-G

Variant summary

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

The NM_052918.5(SORCS1):c.2476-5468G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,110 control chromosomes in the GnomAD database, including 4,808 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 (4808 hom., cov: 33)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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=-0.92).
• 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/exons	MANE	UniProt
SORCS1	NM_052918.5	c.2476-5468G>T		intron_variant		ENST00000263054.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS1	ENST00000263054.11	c.2476-5468G>T		intron_variant		1	NM_052918.5	P1
SORCS1	ENST00000369698.6	c.1208-5468G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34410 AN: 151990 Hom.: 4808 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.175

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: 0.226 AC: 34435 AN: 152110 Hom.: 4808 Cov.: 33 AF XY: 0.230 AC XY: 17069 AN XY: 74362

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.196

Alfa AF: 0.163 Hom.: 4554

Bravo AF: 0.234

Asia WGS AF: 0.405 AC: 1406 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	5.1
Dann	Benign	0.62

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: rs10491052; hg19: chr10-108394614;