7-154361389-C-T

Position:

• chr7-154361389-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.244-84825C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,996 control chromosomes in the GnomAD database, including 21,880 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 0.50 (21880 hom., cov: 32)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_130797.4	c.244-84825C>T		intron_variant		ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.244-84825C>T		intron_variant		1	NM_130797.4	ENSP00000367001

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75643 AN: 151878 Hom.: 21883 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.498 AC: 75643 AN: 151996 Hom.: 21880 Cov.: 32 AF XY: 0.506 AC XY: 37587 AN XY: 74298

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.522

Alfa AF: 0.585 Hom.: 35682

Bravo AF: 0.478

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.79

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: rs12536378; hg19: chr7-154058474;