rs758316

chr7-153934563-G-A

Variant summary

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

The ENST00000404039.5(DPP6):c.51+46829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,974 control chromosomes in the GnomAD database, including 31,051 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 0.63 (31051 hom., cov: 31)
• Consequence: DPP6 ENST00000404039.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_001039350.3	c.51+46829G>A		intron_variant
DPP6	NM_001364497.2	c.60+185555G>A		intron_variant
DPP6	NM_001364498.2	c.60+185555G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000404039.5	c.51+46829G>A		intron_variant		1
DPP6	ENST00000706130.1	c.60+185555G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96219 AN: 151856 Hom.: 31032 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.634 AC: 96282 AN: 151974 Hom.: 31051 Cov.: 31 AF XY: 0.625 AC XY: 46386 AN XY: 74256

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.630

Alfa AF: 0.608 Hom.: 57370

Bravo AF: 0.645

Asia WGS AF: 0.464 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.19
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: rs758316; hg19: chr7-153631648;