chr7-154630460-C-T

Position:

• chr7-154630460-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.628-7361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,052 control chromosomes in the GnomAD database, including 14,307 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 0.42 (14307 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.628-7361C>T		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.628-7361C>T		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64402 AN: 151934 Hom.: 14284 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.424 AC: 64467 AN: 152052 Hom.: 14307 Cov.: 33 AF XY: 0.421 AC XY: 31317 AN XY: 74318

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.408

Alfa AF: 0.383 Hom.: 7304

Bravo AF: 0.424

Asia WGS AF: 0.299 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.33

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: rs6956703; hg19: chr7-154422170; COSMIC: COSV59609777;