rs10509820

Variant names:

• chr10-106763705-C-T
• rs10509820
• NM_052918.5:c.886-2044G>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.886-2044G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 152,244 control chromosomes in the GnomAD database, including 93 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 0.024 (93 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 0 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=-0.87).
• 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.886-2044G>A		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.886-2044G>A		intron_variant	Intron 4 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3580 AN: 152126 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.0453

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00813

Gnomad OTH AF: 0.0224

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

GnomAD4 genome AF: 0.0236 AC: 3586 AN: 152244 Hom.: 93 Cov.: 32 AF XY: 0.0244 AC XY: 1814 AN XY: 74436

African (AFR) AF: 0.0394 AC: 1638 AN: 41544

American (AMR) AF: 0.0179 AC: 273 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0453 AC: 157 AN: 3468

East Asian (EAS) AF: 0.109 AC: 565 AN: 5170

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4822

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10620

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00813 AC: 553 AN: 68016

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.0158 Hom.: 5

Bravo AF: 0.0241

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.77
PhyloP100		0.041
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: rs10509820; hg19: chr10-108523463;