rs10884390

Positions:

• chr10-106949608-G-A

Variant summary

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

The NM_052918.5(SORCS1):​c.626+6905C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,116 control chromosomes in the GnomAD database, including 17,523 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 0.44 (17523 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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 = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.626+6905C>T		intron_variant		ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.626+6905C>T		intron_variant		1	NM_052918.5	ENSP00000263054	P1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67481 AN: 151998 Hom.: 17526 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.444 AC: 67496 AN: 152116 Hom.: 17523 Cov.: 32 AF XY: 0.445 AC XY: 33046 AN XY: 74344

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.471

Alfa AF: 0.548 Hom.: 23065

Bravo AF: 0.412

Asia WGS AF: 0.426 AC: 1481 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	0.20
DANN	Benign	0.83

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: rs10884390; hg19: chr10-108709366;