rs7779540

Positions:

• chr7-153925577-G-A

Variant summary

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

The ENST00000404039.5(DPP6):​c.51+37843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 151,920 control chromosomes in the GnomAD database, including 350 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 0.066 (350 hom., cov: 31)
• Consequence: DPP6 ENST00000404039.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP6	NM_001039350.3	c.51+37843G>A		intron_variant			NP_001034439.1
DPP6	NM_001364497.2	c.60+176569G>A		intron_variant			NP_001351426.1
DPP6	NM_001364498.2	c.60+176569G>A		intron_variant			NP_001351427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000404039.5	c.51+37843G>A		intron_variant		1		ENSP00000385578
DPP6	ENST00000706130.1	c.60+176569G>A		intron_variant				ENSP00000516215

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9975 AN: 151798 Hom.: 350 Cov.: 31

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0599

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

GnomAD4 genome AF: 0.0657 AC: 9981 AN: 151920 Hom.: 350 Cov.: 31 AF XY: 0.0633 AC XY: 4701 AN XY: 74218

Gnomad4 AFR AF: 0.0851

Gnomad4 AMR AF: 0.0600

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0406

Gnomad4 SAS AF: 0.0241

Gnomad4 FIN AF: 0.0511

Gnomad4 NFE AF: 0.0631

Gnomad4 OTH AF: 0.0602

Alfa AF: 0.0591 Hom.: 353

Bravo AF: 0.0679

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.6
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7779540; hg19: chr7-153622662;