7-154270195-G-A

Position:

• chr7-154270195-G-A

Variant summary

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

The NM_130797.4(DPP6):​c.244-176019G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,076 control chromosomes in the GnomAD database, including 2,125 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 0.14 (2125 hom., cov: 32)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

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 = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_130797.4	c.244-176019G>A		intron_variant		ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.244-176019G>A		intron_variant		1	NM_130797.4	ENSP00000367001
DPP6	ENST00000404039.5	c.52-176019G>A		intron_variant		1		ENSP00000385578
DPP6	ENST00000406326.5	c.244-176019G>A		intron_variant		1		ENSP00000384393
DPP6	ENST00000706130.1	c.61-176019G>A		intron_variant				ENSP00000516215

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21815 AN: 151958 Hom.: 2121 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0452

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.144 AC: 21836 AN: 152076 Hom.: 2125 Cov.: 32 AF XY: 0.141 AC XY: 10489 AN XY: 74334

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0474

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.160

Alfa AF: 0.108 Hom.: 1361

Bravo AF: 0.158

Asia WGS AF: 0.116 AC: 405 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	3.6
DANN	Benign	0.80

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: rs10274025; hg19: chr7-153967280; COSMIC: COSV66742896;