rs2316242

Positions:

• chr7-154731136-C-T

Variant summary

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

The NM_130797.4(DPP6):​c.883+3249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,016 control chromosomes in the GnomAD database, including 1,094 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 0.076 (1094 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

Genes affected

DPP6 (HGNC:3010): (dipeptidyl peptidase like 6) This gene encodes a single-pass type II membrane protein that is a member of the peptidase S9B family of serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Variations in this gene may be associated with susceptibility to amyotrophic lateral sclerosis and with idiopathic ventricular fibrillation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.883+3249C>T		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.883+3249C>T		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11449 AN: 151896 Hom.: 1087 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0565

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

GnomAD4 genome AF: 0.0755 AC: 11478 AN: 152016 Hom.: 1094 Cov.: 33 AF XY: 0.0742 AC XY: 5515 AN XY: 74292

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0322 Hom.: 163

Bravo AF: 0.0847

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.091
DANN	Benign	0.55

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: rs2316242; hg19: chr7-154522846;