rs6812745

Variant names:

• chr4-7532876-A-G
• rs6812745
• NM_020777.3:c.648+1247A>G

Variant summary

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

The NM_020777.3(SORCS2):​c.648+1247A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 151,774 control chromosomes in the GnomAD database, including 2,475 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 0.17 (2475 hom., cov: 31)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.648+1247A>G		intron_variant	Intron 3 of 26	ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.648+1247A>G		intron_variant	Intron 3 of 26	1	NM_020777.3	ENSP00000422185.2
SORCS2	ENST00000511199.1	n.263+1247A>G		intron_variant	Intron 3 of 5	4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26229 AN: 151656 Hom.: 2461 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.00658

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.173 AC: 26282 AN: 151774 Hom.: 2475 Cov.: 31 AF XY: 0.169 AC XY: 12501 AN XY: 74134

African (AFR) AF: 0.207 AC: 8554 AN: 41352

American (AMR) AF: 0.195 AC: 2979 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3468

East Asian (EAS) AF: 0.00679 AC: 35 AN: 5156

South Asian (SAS) AF: 0.124 AC: 592 AN: 4784

European-Finnish (FIN) AF: 0.116 AC: 1222 AN: 10554

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.166 AC: 11299 AN: 67902

Other (OTH) AF: 0.177 AC: 373 AN: 2108

Alfa AF: 0.177 Hom.: 6790

Bravo AF: 0.181

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.77
PhyloP100		0.028
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: rs6812745; hg19: chr4-7534603;