rs4725537

chr7-154370458-A-C

Variant summary

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

The NM_130797.4(DPP6):c.244-75756A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,982 control chromosomes in the GnomAD database, including 8,488 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 0.24 (8488 hom., cov: 31)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.244-75756A>C		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.244-75756A>C		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35854 AN: 151864 Hom.: 8453 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0844

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.237 AC: 35948 AN: 151982 Hom.: 8488 Cov.: 31 AF XY: 0.231 AC XY: 17210 AN XY: 74344

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0663

Gnomad4 NFE AF: 0.0844

Gnomad4 OTH AF: 0.209

Alfa AF: 0.107 Hom.: 2224

Bravo AF: 0.257

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	4.7
Dann	Benign	0.52

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: rs4725537; hg19: chr7-154067543;