rs17277986

Positions:

• chr10-106998968-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.559-42388G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,074 control chromosomes in the GnomAD database, including 4,377 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 0.22 (4377 hom., cov: 33)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.559-42388G>A		intron_variant		ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.559-42388G>A		intron_variant		1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33044 AN: 151956 Hom.: 4376 Cov.: 33

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.217 AC: 33043 AN: 152074 Hom.: 4377 Cov.: 33 AF XY: 0.218 AC XY: 16216 AN XY: 74322

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.235

Alfa AF: 0.243 Hom.: 600

Bravo AF: 0.205

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
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: rs17277986; hg19: chr10-108758726;