7-154052206-A-C

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+164472A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 149,518 control chromosomes in the GnomAD database, including 31,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.64 (31397 hom., cov: 31)
• Consequence: DPP6 ENST00000404039.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.96

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=-0.97).
• BP6: Variant 7-154052206-A-C is Benign according to our data. Variant chr7-154052206-A-C is described in ClinVar as [Benign]. Clinvar id is 1274603.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_001039350.3	c.51+164472A>C		intron_variant
DPP6	NM_001364497.2	c.60+303198A>C		intron_variant
DPP6	NM_001364498.2	c.60+303198A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000404039.5	c.51+164472A>C		intron_variant		1
DPP6	ENST00000706130.1	c.60+303198A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.638 AC: 95331 AN: 149408 Hom.: 31336 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.638 AC: 95450 AN: 149518 Hom.: 31397 Cov.: 31 AF XY: 0.642 AC XY: 46828 AN XY: 72982

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.605

Alfa AF: 0.609 Hom.: 3543

Bravo AF: 0.639

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

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.1
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7797494; hg19: chr7-153749291; COSMIC: COSV66731472; COSMIC: COSV66731472;