rs10786981

Variant names:

• chr10-106921972-A-G
• rs10786981
• NM_052918.5:c.626+34541T>C

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+34541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,128 control chromosomes in the GnomAD database, including 22,466 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 (22466 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 2 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=-0.97).
• 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+34541T>C		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.626+34541T>C		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.626+34541T>C		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+34541T>C		intron	N/A	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79629 AN: 152010 Hom.: 22456 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.524 AC: 79681 AN: 152128 Hom.: 22466 Cov.: 32 AF XY: 0.523 AC XY: 38918 AN XY: 74396

African (AFR) AF: 0.310 AC: 12883 AN: 41504

American (AMR) AF: 0.530 AC: 8086 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2330 AN: 5168

South Asian (SAS) AF: 0.535 AC: 2580 AN: 4818

European-Finnish (FIN) AF: 0.682 AC: 7219 AN: 10584

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.628 AC: 42678 AN: 68008

Other (OTH) AF: 0.551 AC: 1161 AN: 2108

Alfa AF: 0.577 Hom.: 14929

Bravo AF: 0.508

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.030
DANN	Benign	0.40
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10786981; hg19: chr10-108681730;