rs4918280

Variant names:

• chr10-107031000-C-T
• rs4918280
• NM_052918.5:c.559-74420G>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.559-74420G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,966 control chromosomes in the GnomAD database, including 19,590 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 0.48 (19590 hom., cov: 32)
• Consequence: SORCS1 NM_052918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• Publications: 5 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)

ENSG00000294532 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	NM_052918.5	MANE Select	c.559-74420G>A		intron	N/A	NP_443150.3
	SORCS1	NM_001387556.1		c.559-74420G>A		intron	N/A	NP_001374485.1
	SORCS1	NM_001013031.3		c.559-74420G>A		intron	N/A	NP_001013049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS1	ENST00000263054.11	TSL:1 MANE Select	c.559-74420G>A		intron	N/A	ENSP00000263054.5
	ENSG00000294532	ENST00000724189.1		n.119+4899C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72810 AN: 151848 Hom.: 19548 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.480 AC: 72919 AN: 151966 Hom.: 19590 Cov.: 32 AF XY: 0.479 AC XY: 35553 AN XY: 74268

African (AFR) AF: 0.743 AC: 30790 AN: 41460

American (AMR) AF: 0.459 AC: 7005 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1537 AN: 5166

South Asian (SAS) AF: 0.342 AC: 1646 AN: 4814

European-Finnish (FIN) AF: 0.407 AC: 4281 AN: 10526

Middle Eastern (MID) AF: 0.383 AC: 111 AN: 290

European-Non Finnish (NFE) AF: 0.364 AC: 24767 AN: 67962

Other (OTH) AF: 0.451 AC: 950 AN: 2106

Alfa AF: 0.407 Hom.: 38224

Bravo AF: 0.499

Asia WGS AF: 0.345 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.068
DANN	Benign	0.60
PhyloP100		-0.74
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: rs4918280; hg19: chr10-108790758;