Genetic Variant NM_130797.4:c.883+3249C>T (chr7-154731136-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_130797.4(DPP6):c.883+3249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,016 control chromosomes in the GnomAD database, including 1,094 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 0.076 ( 1094 hom., cov: 33)

Consequence

DPP6
NM_130797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

3 publications found

Variant links:

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

DPP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4 link	c.883+3249C>T		intron_variant	Intron 8 of 25	ENST00000377770.8	NP_570629.2	P42658-1Q8IYG9A7E2E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8 link	c.883+3249C>T		intron_variant	Intron 8 of 25	1	NM_130797.4	ENSP00000367001.3		P42658-1

Frequencies

GnomAD3 genomes

AF:

0.0754

AC:

11449

AN:

151896

Hom.:

1087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0503

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0638

Gnomad SAS

AF:

0.0419

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0565

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

GnomAD4 genome

AF:

0.0755

AC:

11478

AN:

152016

Hom.:

1094

Cov.:

AF XY:

0.0742

AC XY:

5515

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.223

AC:

9222

AN:

41416

American (AMR)

AF:

0.0510

AC:

780

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.0638

AC:

329

AN:

5158

South Asian (SAS)

AF:

0.0418

AC:

201

AN:

4814

European-Finnish (FIN)

AF:

0.0119

AC:

126

AN:

10568

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0101

AC:

689

AN:

67988

Other (OTH)

AF:

0.0563

AC:

119

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

466

932

1398

1864

2330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0332

Hom.:

254

Bravo

AF:

0.0847

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.091

(source)

DANN

Benign

0.55

PhyloP100

-1.4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over