rs12666280

Positions:

• chr7-154717614-T-C

Variant summary

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

The NM_130797.4(DPP6):​c.763-10153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,162 control chromosomes in the GnomAD database, including 14,972 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 0.40 (14972 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.763-10153T>C		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.763-10153T>C		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61446 AN: 152042 Hom.: 14956 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.404 AC: 61467 AN: 152162 Hom.: 14972 Cov.: 33 AF XY: 0.411 AC XY: 30584 AN XY: 74376

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.455

Alfa AF: 0.489 Hom.: 24212

Bravo AF: 0.395

Asia WGS AF: 0.514 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.42

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: rs12666280; hg19: chr7-154509324;