chr10-106965737-C-T

Variant names:

• chr10-106965737-C-T
• rs4918273
• NM_052918.5:c.559-9157G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387556.1(SORCS1):​c.559-9157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,914 control chromosomes in the GnomAD database, including 25,550 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 0.58 (25550 hom., cov: 31)
• Consequence: SORCS1 NM_001387556.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387556.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	NM_052918.5	MANE Select	c.559-9157G>A		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.559-9157G>A		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.559-9157G>A		intron	N/A	NP_001013049.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.559-9157G>A		intron	N/A	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87608 AN: 151796 Hom.: 25531 Cov.: 31

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.577 AC: 87676 AN: 151914 Hom.: 25550 Cov.: 31 AF XY: 0.576 AC XY: 42740 AN XY: 74224

African (AFR) AF: 0.516 AC: 21346 AN: 41396

American (AMR) AF: 0.556 AC: 8488 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2037 AN: 3464

East Asian (EAS) AF: 0.635 AC: 3276 AN: 5162

South Asian (SAS) AF: 0.520 AC: 2502 AN: 4814

European-Finnish (FIN) AF: 0.644 AC: 6791 AN: 10544

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.606 AC: 41156 AN: 67950

Other (OTH) AF: 0.588 AC: 1241 AN: 2112

Alfa AF: 0.596 Hom.: 13419

Bravo AF: 0.570

Asia WGS AF: 0.543 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.36
PhyloP100		-0.28
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: rs4918273; hg19: chr10-108725495;