7-154052119-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000404039.5(DPP6):c.51+164385C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 148,078 control chromosomes in the GnomAD database, including 19,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (19155 hom., cov: 31)
• Consequence: DPP6 ENST00000404039.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-154052119-C-G is Benign according to our data. Variant chr7-154052119-C-G is described in ClinVar as [Benign]. Clinvar id is 1232875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_001039350.3	c.51+164385C>G		intron_variant
DPP6	NM_001364497.2	c.60+303111C>G		intron_variant
DPP6	NM_001364498.2	c.60+303111C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000404039.5	c.51+164385C>G		intron_variant		1
DPP6	ENST00000706130.1	c.60+303111C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.498 AC: 73684 AN: 147974 Hom.: 19154 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.498 AC: 73704 AN: 148078 Hom.: 19155 Cov.: 31 AF XY: 0.502 AC XY: 36272 AN XY: 72230

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.492

Alfa AF: 0.510 Hom.: 2514

Bravo AF: 0.483

Asia WGS AF: 0.562 AC: 1928 AN: 3428

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.1
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200027945; hg19: chr7-153749204; COSMIC: COSV66751769; COSMIC: COSV66751769;