chr10-107119851-C-T

Variant names:

• chr10-107119851-C-T
• rs625792
• NM_052918.5:c.558+44118G>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.558+44118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 151,982 control chromosomes in the GnomAD database, including 46,153 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 0.77 (46153 hom., cov: 31)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.558+44118G>A		intron_variant	Intron 1 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.558+44118G>A		intron_variant	Intron 1 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116815 AN: 151864 Hom.: 46108 Cov.: 31

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.769 AC: 116904 AN: 151982 Hom.: 46153 Cov.: 31 AF XY: 0.762 AC XY: 56593 AN XY: 74248

African (AFR) AF: 0.936 AC: 38862 AN: 41508

American (AMR) AF: 0.649 AC: 9897 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2612 AN: 3466

East Asian (EAS) AF: 0.551 AC: 2842 AN: 5156

South Asian (SAS) AF: 0.519 AC: 2498 AN: 4812

European-Finnish (FIN) AF: 0.729 AC: 7668 AN: 10522

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 49992 AN: 67948

Other (OTH) AF: 0.760 AC: 1602 AN: 2108

Alfa AF: 0.757 Hom.: 11709

Bravo AF: 0.776

Asia WGS AF: 0.540 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.44
PhyloP100		-0.81
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: rs625792; hg19: chr10-108879609;