rs3807243

Positions:

• chr7-154691027-G-A

Variant summary

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

The NM_130797.4(DPP6):​c.762+21586G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,034 control chromosomes in the GnomAD database, including 2,519 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 0.16 (2519 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.762+21586G>A		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.762+21586G>A		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24821 AN: 151916 Hom.: 2507 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.164 AC: 24861 AN: 152034 Hom.: 2519 Cov.: 33 AF XY: 0.161 AC XY: 11940 AN XY: 74344

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0763

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.133

Alfa AF: 0.159 Hom.: 359

Bravo AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.66

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: rs3807243; hg19: chr7-154482737;