rs600879

chr10-107163360-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.558+609G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,122 control chromosomes in the GnomAD database, including 2,742 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 0.16 (2742 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS1	NM_052918.5	c.558+609G>A		intron_variant		ENST00000263054.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS1	ENST00000263054.11	c.558+609G>A		intron_variant		1	NM_052918.5	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24300 AN: 152004 Hom.: 2732 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.0833

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.160 AC: 24343 AN: 152122 Hom.: 2742 Cov.: 32 AF XY: 0.155 AC XY: 11526 AN XY: 74370

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.0831

Gnomad4 SAS AF: 0.0419

Gnomad4 FIN AF: 0.0762

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.146

Alfa AF: 0.126 Hom.: 335

Bravo AF: 0.172

Asia WGS AF: 0.0700 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	8.5
Dann	Benign	0.80

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: rs600879; hg19: chr10-108923118;