chr4-7736642-T-C

Variant names:

• chr4-7736642-T-C
• rs886374
• NM_020777.3:c.3312-427T>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.3312-427T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,076 control chromosomes in the GnomAD database, including 39,255 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 0.72 (39255 hom., cov: 33)
• Consequence: SORCS2 NM_020777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020777.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS2	NM_020777.3	MANE Select	c.3312-427T>C		intron	N/A	NP_065828.2	Q96PQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORCS2	ENST00000507866.6	TSL:1 MANE Select	c.3312-427T>C		intron	N/A	ENSP00000422185.2	Q96PQ0
	SORCS2	ENST00000505529.1	TSL:4	c.96-427T>C		intron	N/A	ENSP00000424194.1	H0Y9I2

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109069 AN: 151958 Hom.: 39230 Cov.: 33

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.718 AC: 109148 AN: 152076 Hom.: 39255 Cov.: 33 AF XY: 0.719 AC XY: 53475 AN XY: 74342

African (AFR) AF: 0.688 AC: 28524 AN: 41488

American (AMR) AF: 0.747 AC: 11424 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2446 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3426 AN: 5132

South Asian (SAS) AF: 0.722 AC: 3477 AN: 4818

European-Finnish (FIN) AF: 0.759 AC: 8036 AN: 10582

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.729 AC: 49530 AN: 67976

Other (OTH) AF: 0.685 AC: 1442 AN: 2106

Alfa AF: 0.716 Hom.: 57929

Bravo AF: 0.713

Asia WGS AF: 0.707 AC: 2457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.56
PhyloP100		-0.79
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: rs886374; hg19: chr4-7738369;