rs4726409

Variant names:

• chr7-154333738-G-A
• rs4726409
• NM_130797.4:c.244-112476G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-154333738-G-A
• chr7-154333738-G-C
• chr7-154333738-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130797.4(DPP6):​c.244-112476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,068 control chromosomes in the GnomAD database, including 14,478 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 0.40 (14478 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 1 publications found

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]

DPP6 Gene-Disease associations (from GenCC):

• autosomal dominant primary microcephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• paroxysmal familial ventricular fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal dominant 33

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• ventricular fibrillation, paroxysmal familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.244-112476G>A		intron_variant	Intron 1 of 25	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.244-112476G>A		intron_variant	Intron 1 of 25	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60965 AN: 151950 Hom.: 14470 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.401 AC: 60978 AN: 152068 Hom.: 14478 Cov.: 33 AF XY: 0.410 AC XY: 30514 AN XY: 74336

African (AFR) AF: 0.137 AC: 5682 AN: 41490

American (AMR) AF: 0.472 AC: 7215 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1679 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3320 AN: 5172

South Asian (SAS) AF: 0.391 AC: 1881 AN: 4812

European-Finnish (FIN) AF: 0.605 AC: 6401 AN: 10578

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33229 AN: 67954

Other (OTH) AF: 0.398 AC: 840 AN: 2112

Alfa AF: 0.464 Hom.: 10164

Bravo AF: 0.381

Asia WGS AF: 0.474 AC: 1648 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.034
DANN	Benign	0.59
PhyloP100		-1.8

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

Other links and lift over

dbSNP: rs4726409; hg19: chr7-154030823;