4-7473697-G-A

Variant names:

• chr4-7473697-G-A
• rs7683874
• NM_020777.3:c.549-57833G>A

Variant summary

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

The NM_020777.3(SORCS2):​c.549-57833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,038 control chromosomes in the GnomAD database, including 1,952 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 0.14 (1952 hom., cov: 32)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.549-57833G>A		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.549-57833G>A		intron_variant	Intron 2 of 26	1	NM_020777.3	ENSP00000422185.2
SORCS2	ENST00000511199.1	n.164-57833G>A		intron_variant	Intron 2 of 5	4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20882 AN: 151918 Hom.: 1944 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0625

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.138 AC: 20917 AN: 152038 Hom.: 1952 Cov.: 32 AF XY: 0.142 AC XY: 10561 AN XY: 74326

African (AFR) AF: 0.242 AC: 10023 AN: 41456

American (AMR) AF: 0.170 AC: 2601 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1181 AN: 5126

South Asian (SAS) AF: 0.245 AC: 1174 AN: 4800

European-Finnish (FIN) AF: 0.105 AC: 1108 AN: 10594

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0625 AC: 4248 AN: 67992

Other (OTH) AF: 0.125 AC: 264 AN: 2106

Alfa AF: 0.0863 Hom.: 3734

Bravo AF: 0.144

Asia WGS AF: 0.254 AC: 882 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	7.8
DANN	Benign	0.80
PhyloP100		0.24
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: rs7683874; hg19: chr4-7475424;