rs6952728

Positions:

• chr7-154594309-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.627+27393C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,128 control chromosomes in the GnomAD database, including 3,876 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 0.18 (3876 hom., cov: 32)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.627+27393C>T		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.627+27393C>T		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27382 AN: 152010 Hom.: 3862 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.180 AC: 27441 AN: 152128 Hom.: 3876 Cov.: 32 AF XY: 0.177 AC XY: 13168 AN XY: 74384

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0702

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.166

Alfa AF: 0.119 Hom.: 1421

Bravo AF: 0.201

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.61

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: rs6952728; hg19: chr7-154386019;