10-106971929-T-C

Position:

• chr10-106971929-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.559-15349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,150 control chromosomes in the GnomAD database, including 3,307 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 0.19 (3307 hom., cov: 31)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.559-15349A>G		intron_variant		ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.559-15349A>G		intron_variant		1	NM_052918.5	ENSP00000263054	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29070 AN: 152032 Hom.: 3307 Cov.: 31

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.191 AC: 29068 AN: 152150 Hom.: 3307 Cov.: 31 AF XY: 0.194 AC XY: 14402 AN XY: 74382

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.214

Alfa AF: 0.207 Hom.: 597

Bravo AF: 0.180

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.022
DANN	Benign	0.78

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: rs2900717; hg19: chr10-108731687; COSMIC: COSV53899332; COSMIC: COSV53899332;