rs12500759

Variant names:

• chr4-7708153-C-T
• rs12500759
• NM_020777.3:c.1868+3869C>T

Variant summary

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

The NM_020777.3(SORCS2):​c.1868+3869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,148 control chromosomes in the GnomAD database, including 5,169 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 0.25 (5169 hom., cov: 33)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORCS2	NM_020777.3	c.1868+3869C>T		intron_variant	Intron 14 of 26	ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORCS2	ENST00000507866.6	c.1868+3869C>T		intron_variant	Intron 14 of 26	1	NM_020777.3	ENSP00000422185.2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38342 AN: 152030 Hom.: 5167 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.252 AC: 38360 AN: 152148 Hom.: 5169 Cov.: 33 AF XY: 0.253 AC XY: 18784 AN XY: 74392

African (AFR) AF: 0.145 AC: 6040 AN: 41524

American (AMR) AF: 0.246 AC: 3769 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3466

East Asian (EAS) AF: 0.337 AC: 1738 AN: 5162

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4816

European-Finnish (FIN) AF: 0.294 AC: 3119 AN: 10592

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20506 AN: 67978

Other (OTH) AF: 0.233 AC: 492 AN: 2114

Alfa AF: 0.282 Hom.: 10503

Bravo AF: 0.242

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.55
PhyloP100		1.0
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: rs12500759; hg19: chr4-7709880;