4-7218206-T-G

Position:

• chr4-7218206-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020777.3(SORCS2):​c.480+25080T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,044 control chromosomes in the GnomAD database, including 32,076 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 0.65 (32076 hom., cov: 32)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.480+25080T>G		intron_variant		ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.480+25080T>G		intron_variant		1	NM_020777.3	ENSP00000422185	P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98432 AN: 151926 Hom.: 32043 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.648 AC: 98521 AN: 152044 Hom.: 32076 Cov.: 32 AF XY: 0.648 AC XY: 48199 AN XY: 74328

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.651

Alfa AF: 0.615 Hom.: 30010

Bravo AF: 0.655

Asia WGS AF: 0.706 AC: 2456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.0
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs4234798; hg19: chr4-7219933;