7-154860569-C-T

Position:

• chr7-154860569-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.1714+6742C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,184 control chromosomes in the GnomAD database, including 2,181 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 0.15 (2181 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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]

ENSG00000236408 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_130797.4	c.1714+6742C>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.1714+6742C>T		intron_variant		1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23414 AN: 152066 Hom.: 2178 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.154 AC: 23425 AN: 152184 Hom.: 2181 Cov.: 33 AF XY: 0.159 AC XY: 11826 AN XY: 74404

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.152

Alfa AF: 0.125 Hom.: 1356

Bravo AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.28
DANN	Benign	0.37

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: rs878742; hg19: chr7-154652279;