rs11767658

chr7-154640535-T-Achr7-154640535-T-G

Variant summary

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

The NM_130797.4(DPP6):c.680+2662T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,968 control chromosomes in the GnomAD database, including 10,587 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 0.37 (10587 hom., cov: 32)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.688

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.680+2662T>A		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.680+2662T>A		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56295 AN: 151850 Hom.: 10582 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.371 AC: 56326 AN: 151968 Hom.: 10587 Cov.: 32 AF XY: 0.369 AC XY: 27412 AN XY: 74294

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.352

Alfa AF: 0.255 Hom.: 618

Bravo AF: 0.368

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.0
Dann	Benign	0.77

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: rs11767658; hg19: chr7-154432245;