rs2046748

Positions:

• chr7-154622300-G-A
• chr7-154622300-G-C

Variant summary

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

The NM_130797.4(DPP6):​c.628-15521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,154 control chromosomes in the GnomAD database, including 53,454 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 0.83 (53454 hom., cov: 32)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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]

LOC105375581 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.628-15521G>A		intron_variant		ENST00000377770.8
LOC105375581	XR_007060600.1	n.221+98C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.628-15521G>A		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126584 AN: 152036 Hom.: 53431 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.832 AC: 126654 AN: 152154 Hom.: 53454 Cov.: 32 AF XY: 0.828 AC XY: 61555 AN XY: 74384

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.844

Alfa AF: 0.880 Hom.: 79201

Bravo AF: 0.825

Asia WGS AF: 0.605 AC: 2104 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	2.9
DANN	Benign	0.79

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: rs2046748; hg19: chr7-154414010;