rs887107

chr7-153942476-T-C

Variant summary

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

The ENST00000404039.5(DPP6):c.51+54742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,108 control chromosomes in the GnomAD database, including 6,296 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 0.28 (6296 hom., cov: 34)
• Consequence: DPP6 ENST00000404039.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_001039350.3	c.51+54742T>C		intron_variant
DPP6	NM_001364497.2	c.60+193468T>C		intron_variant
DPP6	NM_001364498.2	c.60+193468T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000404039.5	c.51+54742T>C		intron_variant		1
DPP6	ENST00000706130.1	c.60+193468T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42298 AN: 151990 Hom.: 6294 Cov.: 34

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.278 AC: 42318 AN: 152108 Hom.: 6296 Cov.: 34 AF XY: 0.273 AC XY: 20301 AN XY: 74362

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.0854

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.273

Alfa AF: 0.268 Hom.: 3088

Bravo AF: 0.279

Asia WGS AF: 0.159 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.4
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs887107; hg19: chr7-153639561;