4-7464739-T-C

Variant names:

• chr4-7464739-T-C
• rs4411993
• NM_020777.3:c.549-66791T>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.549-66791T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,284 control chromosomes in the GnomAD database, including 60,529 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 0.89 (60529 hom., cov: 33)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.549-66791T>C		intron_variant	Intron 2 of 26	ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.549-66791T>C		intron_variant	Intron 2 of 26	1	NM_020777.3	ENSP00000422185.2
SORCS2	ENST00000511199.1	n.164-66791T>C		intron_variant	Intron 2 of 5	4

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135350 AN: 152166 Hom.: 60471 Cov.: 33

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.882

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.890 AC: 135466 AN: 152284 Hom.: 60529 Cov.: 33 AF XY: 0.886 AC XY: 65933 AN XY: 74454

African (AFR) AF: 0.959 AC: 39855 AN: 41572

American (AMR) AF: 0.887 AC: 13578 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2996 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3972 AN: 5166

South Asian (SAS) AF: 0.734 AC: 3538 AN: 4820

European-Finnish (FIN) AF: 0.857 AC: 9087 AN: 10604

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.875 AC: 59539 AN: 68032

Other (OTH) AF: 0.866 AC: 1828 AN: 2112

Alfa AF: 0.877 Hom.: 99916

Bravo AF: 0.898

Asia WGS AF: 0.764 AC: 2657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.41
PhyloP100		-0.29
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: rs4411993; hg19: chr4-7466466;