rs7694661

Positions:

• chr4-7422024-C-A

Variant summary

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

The NM_020777.3(SORCS2):​c.548+25669C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,942 control chromosomes in the GnomAD database, including 10,554 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 0.37 (10554 hom., cov: 32)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORCS2	NM_020777.3	c.548+25669C>A		intron_variant		ENST00000507866.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORCS2	ENST00000507866.6	c.548+25669C>A		intron_variant		1	NM_020777.3	P1
SORCS2	ENST00000511199.1	n.163+25669C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55722 AN: 151824 Hom.: 10547 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.367 AC: 55759 AN: 151942 Hom.: 10554 Cov.: 32 AF XY: 0.368 AC XY: 27300 AN XY: 74278

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.355

Alfa AF: 0.334 Hom.: 5574

Bravo AF: 0.372

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.42

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: rs7694661; hg19: chr4-7423751;