7-154677266-A-G

Position:

• chr7-154677266-A-G

Variant summary

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

The NM_130797.4(DPP6):​c.762+7825A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,126 control chromosomes in the GnomAD database, including 1,208 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 0.12 (1208 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_130797.4	c.762+7825A>G		intron_variant		ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.762+7825A>G		intron_variant		1	NM_130797.4	ENSP00000367001

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18393 AN: 152008 Hom.: 1205 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.121 AC: 18414 AN: 152126 Hom.: 1208 Cov.: 33 AF XY: 0.122 AC XY: 9105 AN XY: 74350

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0784

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0698

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.119

Alfa AF: 0.104 Hom.: 1812

Bravo AF: 0.115

Asia WGS AF: 0.0610 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.28

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: rs916514; hg19: chr7-154468976;