chr7-154513713-T-C

Variant names:

• chr7-154513713-T-C
• rs10260404
• NM_130797.4:c.458-26819T>C

Variant summary

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

The NM_130797.4(DPP6):​c.458-26819T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,952 control chromosomes in the GnomAD database, including 9,478 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 0.35 (9478 hom., cov: 31)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• Publications: 37 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.458-26819T>C		intron_variant	Intron 3 of 25	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.458-26819T>C		intron_variant	Intron 3 of 25	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53337 AN: 151834 Hom.: 9469 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.351 AC: 53379 AN: 151952 Hom.: 9478 Cov.: 31 AF XY: 0.349 AC XY: 25938 AN XY: 74258

African (AFR) AF: 0.336 AC: 13925 AN: 41440

American (AMR) AF: 0.302 AC: 4623 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3468

East Asian (EAS) AF: 0.171 AC: 881 AN: 5148

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4816

European-Finnish (FIN) AF: 0.379 AC: 3993 AN: 10546

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25832 AN: 67938

Other (OTH) AF: 0.351 AC: 740 AN: 2106

Alfa AF: 0.368 Hom.: 45350

Bravo AF: 0.345

Asia WGS AF: 0.268 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.070
DANN	Benign	0.42
PhyloP100		-3.3

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: rs10260404; hg19: chr7-154210798;