10-106971929-T-C

Variant names:

• chr10-106971929-T-C
• rs2900717
• NM_052918.5:c.559-15349A>G

Variant summary

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

The NM_052918.5(SORCS1):​c.559-15349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,150 control chromosomes in the GnomAD database, including 3,307 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 0.19 (3307 hom., cov: 31)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.559-15349A>G		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.559-15349A>G		intron_variant	Intron 1 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29070 AN: 152032 Hom.: 3307 Cov.: 31

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.191 AC: 29068 AN: 152150 Hom.: 3307 Cov.: 31 AF XY: 0.194 AC XY: 14402 AN XY: 74382

African (AFR) AF: 0.0659 AC: 2736 AN: 41546

American (AMR) AF: 0.191 AC: 2911 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1082 AN: 5176

South Asian (SAS) AF: 0.296 AC: 1429 AN: 4820

European-Finnish (FIN) AF: 0.240 AC: 2532 AN: 10562

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16582 AN: 67980

Other (OTH) AF: 0.214 AC: 453 AN: 2112

Alfa AF: 0.203 Hom.: 599

Bravo AF: 0.180

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.022
DANN	Benign	0.78
PhyloP100		-2.3
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: rs2900717; hg19: chr10-108731687; COSMIC: COSV53899332; COSMIC: COSV53899332;