rs7083707

Positions:

• chr10-107130668-T-C

Variant summary

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

The NM_052918.5(SORCS1):​c.558+33301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 151,956 control chromosomes in the GnomAD database, including 651 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 0.087 (651 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS1	NM_052918.5	c.558+33301A>G		intron_variant		ENST00000263054.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS1	ENST00000263054.11	c.558+33301A>G		intron_variant		1	NM_052918.5	P1

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13131 AN: 151842 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0839

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0866 AC: 13153 AN: 151956 Hom.: 651 Cov.: 32 AF XY: 0.0855 AC XY: 6351 AN XY: 74258

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.0651

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0703 Hom.: 554

Bravo AF: 0.0900

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.066
DANN	Benign	0.42

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: rs7083707; hg19: chr10-108890426;