rs3846421

Variant names:

• chr4-7283629-G-A
• rs3846421
• NM_020777.3:c.480+90503G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-7283629-G-A
• chr4-7283629-G-C

Variant summary

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

The NM_020777.3(SORCS2):​c.480+90503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,018 control chromosomes in the GnomAD database, including 34,692 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 0.67 (34692 hom., cov: 32)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 4 publications found

Genes affected

SORCS2 (HGNC:16698): (sortilin related VPS10 domain containing receptor 2) 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. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.480+90503G>A		intron_variant	Intron 1 of 26	ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.480+90503G>A		intron_variant	Intron 1 of 26	1	NM_020777.3	ENSP00000422185.2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102473 AN: 151900 Hom.: 34652 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.675 AC: 102561 AN: 152018 Hom.: 34692 Cov.: 32 AF XY: 0.677 AC XY: 50323 AN XY: 74328

African (AFR) AF: 0.667 AC: 27627 AN: 41428

American (AMR) AF: 0.766 AC: 11720 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3470

East Asian (EAS) AF: 0.682 AC: 3519 AN: 5162

South Asian (SAS) AF: 0.580 AC: 2792 AN: 4814

European-Finnish (FIN) AF: 0.700 AC: 7403 AN: 10574

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45098 AN: 67958

Other (OTH) AF: 0.682 AC: 1438 AN: 2108

Alfa AF: 0.659 Hom.: 17367

Bravo AF: 0.681

Asia WGS AF: 0.637 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.065
DANN	Benign	0.45
PhyloP100		-1.3
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: rs3846421; hg19: chr4-7285356;