rs10509821

Variant names:

• chr10-106775248-T-C
• rs10509821
• NM_052918.5:c.885+1286A>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.885+1286A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,336 control chromosomes in the GnomAD database, including 272 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 0.047 (272 hom., cov: 33)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• 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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.885+1286A>G		intron_variant	Intron 4 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.885+1286A>G		intron_variant	Intron 4 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7146 AN: 152220 Hom.: 272 Cov.: 33

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0416

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

GnomAD4 genome AF: 0.0470 AC: 7167 AN: 152336 Hom.: 272 Cov.: 33 AF XY: 0.0462 AC XY: 3440 AN XY: 74504

African (AFR) AF: 0.0900 AC: 3742 AN: 41580

American (AMR) AF: 0.0295 AC: 452 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 207 AN: 3472

East Asian (EAS) AF: 0.109 AC: 566 AN: 5182

South Asian (SAS) AF: 0.0696 AC: 336 AN: 4826

European-Finnish (FIN) AF: 0.00668 AC: 71 AN: 10626

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0246 AC: 1670 AN: 68022

Other (OTH) AF: 0.0436 AC: 92 AN: 2112

Alfa AF: 0.0397 Hom.: 22

Bravo AF: 0.0496

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		0.12
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: rs10509821; hg19: chr10-108535006;