chr10-106926307-C-T

Variant names:

• chr10-106926307-C-T
• rs10884381
• NM_052918.5:c.626+30206G>A

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+30206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,078 control chromosomes in the GnomAD database, including 22,413 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 0.52 (22413 hom., cov: 33)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	NM_052918.5	MANE Select	c.626+30206G>A		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.626+30206G>A		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.626+30206G>A		intron	N/A	NP_001013049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.626+30206G>A		intron	N/A	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79514 AN: 151960 Hom.: 22403 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.523 AC: 79564 AN: 152078 Hom.: 22413 Cov.: 33 AF XY: 0.523 AC XY: 38852 AN XY: 74342

African (AFR) AF: 0.309 AC: 12809 AN: 41484

American (AMR) AF: 0.529 AC: 8089 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1849 AN: 3460

East Asian (EAS) AF: 0.447 AC: 2314 AN: 5174

South Asian (SAS) AF: 0.534 AC: 2575 AN: 4818

European-Finnish (FIN) AF: 0.683 AC: 7222 AN: 10574

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42660 AN: 67970

Other (OTH) AF: 0.547 AC: 1154 AN: 2110

Alfa AF: 0.597 Hom.: 14137

Bravo AF: 0.507

Asia WGS AF: 0.477 AC: 1658 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.63
PhyloP100		0.041
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: rs10884381; hg19: chr10-108686065;