XM_017015617.1:c.3+6951A>G

Variant names:

• chr10-107174113-T-C
• rs7922128
• XM_017015617.1:c.3+6951A>G

Variant summary

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

The XM_017015617.1(SORCS1):​c.3+6951A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,184 control chromosomes in the GnomAD database, including 1,042 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 0.12 (1042 hom., cov: 32)
• Consequence: SORCS1 XM_017015617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17487 AN: 152064 Hom.: 1037 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0957

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.0924

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.115 AC: 17512 AN: 152184 Hom.: 1042 Cov.: 32 AF XY: 0.115 AC XY: 8578 AN XY: 74408

African (AFR) AF: 0.102 AC: 4218 AN: 41524

American (AMR) AF: 0.0957 AC: 1463 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3472

East Asian (EAS) AF: 0.0970 AC: 503 AN: 5186

South Asian (SAS) AF: 0.0926 AC: 446 AN: 4814

European-Finnish (FIN) AF: 0.146 AC: 1549 AN: 10586

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8460 AN: 68000

Other (OTH) AF: 0.120 AC: 252 AN: 2108

Alfa AF: 0.121 Hom.: 590

Bravo AF: 0.110

Asia WGS AF: 0.0960 AC: 331 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.68
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7922128; hg19: chr10-108933871;