rs38993

Positions:

• chr7-153879172-G-A

Variant summary

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

The NM_001364497.2(DPP6):​c.60+130164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,702 control chromosomes in the GnomAD database, including 27,754 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 0.60 (27754 hom., cov: 30)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

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 = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_001364497.2	c.60+130164G>A		intron_variant
DPP6	NM_001364498.2	c.60+130164G>A		intron_variant
DPP6	NM_001364499.2	c.60+130164G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000706130.1	c.60+130164G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91119 AN: 151584 Hom.: 27728 Cov.: 30

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.601 AC: 91194 AN: 151702 Hom.: 27754 Cov.: 30 AF XY: 0.592 AC XY: 43909 AN XY: 74114

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.579

Alfa AF: 0.602 Hom.: 14016

Bravo AF: 0.608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs38993; hg19: chr7-153576257;