10-106793863-C-G

Position:

• chr10-106793863-C-G

Variant summary

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

The NM_052918.5(SORCS1):​c.727-17171G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,036 control chromosomes in the GnomAD database, including 6,961 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 0.30 (6961 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS1	NM_052918.5	c.727-17171G>C		intron_variant		ENST00000263054.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS1	ENST00000263054.11	c.727-17171G>C		intron_variant		1	NM_052918.5	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45405 AN: 151918 Hom.: 6948 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.299 AC: 45472 AN: 152036 Hom.: 6961 Cov.: 32 AF XY: 0.296 AC XY: 22020 AN XY: 74290

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.275

Alfa AF: 0.171 Hom.: 332

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.69

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: rs11193054; hg19: chr10-108553621;