rs7089127

Positions:

• chr10-107118858-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+45111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,214 control chromosomes in the GnomAD database, including 340 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 0.064 (340 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS1	NM_052918.5	c.558+45111A>G		intron_variant		ENST00000263054.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS1	ENST00000263054.11	c.558+45111A>G		intron_variant		1	NM_052918.5	P1

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9816 AN: 152096 Hom.: 339 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0990

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0773

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0645 AC: 9814 AN: 152214 Hom.: 340 Cov.: 32 AF XY: 0.0646 AC XY: 4811 AN XY: 74418

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.0553

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.0262

Gnomad4 FIN AF: 0.0990

Gnomad4 NFE AF: 0.0773

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0703 Hom.: 210

Bravo AF: 0.0604

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.028
DANN	Benign	0.50

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: rs7089127; hg19: chr10-108878616;