NM_052918.5:c.727-19508G>A

Variant names:

• chr10-106796200-C-T
• rs10509824
• NM_052918.5:c.727-19508G>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.727-19508G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 152,206 control chromosomes in the GnomAD database, including 203 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 0.042 (203 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS1	NM_052918.5	c.727-19508G>A		intron_variant	Intron 3 of 25	ENST00000263054.11	NP_443150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS1	ENST00000263054.11	c.727-19508G>A		intron_variant	Intron 3 of 25	1	NM_052918.5	ENSP00000263054.5

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6327 AN: 152088 Hom.: 203 Cov.: 32

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.00660

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0416 AC: 6336 AN: 152206 Hom.: 203 Cov.: 32 AF XY: 0.0412 AC XY: 3065 AN XY: 74428

African (AFR) AF: 0.0749 AC: 3108 AN: 41516

American (AMR) AF: 0.0259 AC: 395 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3468

East Asian (EAS) AF: 0.107 AC: 551 AN: 5170

South Asian (SAS) AF: 0.0618 AC: 298 AN: 4824

European-Finnish (FIN) AF: 0.00660 AC: 70 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0242 AC: 1643 AN: 68028

Other (OTH) AF: 0.0374 AC: 79 AN: 2112

Alfa AF: 0.0262 Hom.: 71

Bravo AF: 0.0430

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.20
PhyloP100		-1.0
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: rs10509824; hg19: chr10-108555958;