rs1047053

Positions:

• chr7-154893261-G-A
• chr7-154893261-G-T

Variant summary

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

The NM_130797.4(DPP6):​c.*781G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 252,728 control chromosomes in the GnomAD database, including 85,567 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 0.84 (54228 hom., cov: 27)
  • Exomes 𝑓: 0.78 (31339 hom.)
• Consequence: DPP6 NM_130797.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_130797.4	c.*781G>A		3_prime_UTR_variant	26/26	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.*781G>A		3_prime_UTR_variant	26/26	1	NM_130797.4	ENSP00000367001

Frequencies

GnomAD3 genomes AF: 0.843 AC: 127658 AN: 151520 Hom.: 54167 Cov.: 27

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.821

GnomAD4 exome AF: 0.783 AC: 79186 AN: 101092 Hom.: 31339 Cov.: 0 AF XY: 0.779 AC XY: 42357 AN XY: 54388

Gnomad4 AFR exome AF: 0.955

Gnomad4 AMR exome AF: 0.854

Gnomad4 ASJ exome AF: 0.805

Gnomad4 EAS exome AF: 0.702

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.781

Gnomad4 OTH exome AF: 0.793

GnomAD4 genome AF: 0.843 AC: 127779 AN: 151636 Hom.: 54228 Cov.: 27 AF XY: 0.843 AC XY: 62449 AN XY: 74064

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.822

Alfa AF: 0.802 Hom.: 52761

Bravo AF: 0.846

Asia WGS AF: 0.791 AC: 2751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.76

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: rs1047053; hg19: chr7-154684971;