rs4726409

chr7-154333738-G-Achr7-154333738-G-Cchr7-154333738-G-T

Variant summary

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

The NM_130797.4(DPP6):c.244-112476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,068 control chromosomes in the GnomAD database, including 14,478 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 0.40 (14478 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.244-112476G>A		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.244-112476G>A		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60965 AN: 151950 Hom.: 14470 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.401 AC: 60978 AN: 152068 Hom.: 14478 Cov.: 33 AF XY: 0.410 AC XY: 30514 AN XY: 74336

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.398

Alfa AF: 0.463 Hom.: 9292

Bravo AF: 0.381

Asia WGS AF: 0.474 AC: 1648 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.034
Dann	Benign	0.59

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: rs4726409; hg19: chr7-154030823;