4-7376780-T-G

Variant names:

• chr4-7376780-T-G
• rs10516185
• NM_020777.3:c.481-19508T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020777.3(SORCS2):​c.481-19508T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000839 in 150,258 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00084 (0 hom., cov: 34)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.481-19508T>G		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.481-19508T>G		intron_variant	Intron 1 of 26	1	NM_020777.3	ENSP00000422185.2

Frequencies

GnomAD3 genomes AF: 0.000846 AC: 127 AN: 150140 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000468

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000488

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

GnomAD4 genome AF: 0.000839 AC: 126 AN: 150258 Hom.: 0 Cov.: 34 AF XY: 0.000873 AC XY: 64 AN XY: 73330

African (AFR) AF: 0.00285 AC: 117 AN: 41084

American (AMR) AF: 0.000468 AC: 7 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67380

Other (OTH) AF: 0.000483 AC: 1 AN: 2072

Alfa AF: 0.00 Hom.: 53

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.45
DANN	Benign	0.33
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs10516185; hg19: chr4-7378507;