rs4918274

Positions:

• chr10-106970202-G-A

Variant summary

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

The ENST00000263054.11(SORCS1):​c.559-13622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,024 control chromosomes in the GnomAD database, including 3,581 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 0.20 (3580 hom., cov: 31)
  • Exomes 𝑓: 0.18 (1 hom.)
• Consequence: SORCS1 ENST00000263054.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.559-13622C>T		intron_variant		ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.559-13622C>T		intron_variant		1	NM_052918.5	ENSP00000263054	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30246 AN: 151886 Hom.: 3579 Cov.: 31

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.182 AC: 4 AN: 22 Hom.: 1 AF XY: 0.143 AC XY: 2 AN XY: 14

Gnomad4 NFE exome AF: 0.182

GnomAD4 genome AF: 0.199 AC: 30240 AN: 152002 Hom.: 3580 Cov.: 31 AF XY: 0.202 AC XY: 14971 AN XY: 74262

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.222

Alfa AF: 0.247 Hom.: 6639

Bravo AF: 0.188

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.79

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: rs4918274; hg19: chr10-108729960;