rs10884390

Variant names:

• chr10-106949608-G-A
• rs10884390
• NM_052918.5:c.626+6905C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

SORCS1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.626+6905C>T		intron_variant	Intron 2 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.626+6905C>T		intron_variant	Intron 2 of 25	1	NM_052918.5	ENSP00000263054.5

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

African (AFR) AF: 0.176 AC: 7313 AN: 41506

American (AMR) AF: 0.403 AC: 6155 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1799 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1553 AN: 5166

South Asian (SAS) AF: 0.542 AC: 2617 AN: 4826

European-Finnish (FIN) AF: 0.634 AC: 6717 AN: 10588

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39547 AN: 67966

Other (OTH) AF: 0.471 AC: 993 AN: 2110

Alfa AF: 0.530 Hom.: 28871

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
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10884390; hg19: chr10-108709366;