Genetic Variant NM_130797.4:c.457+23879T>G (chr7-154498916-T-G) – 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.457+23879T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,102 control chromosomes in the GnomAD database, including 4,236 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 0.22 ( 4236 hom., cov: 32)

Consequence

DPP6
NM_130797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.317

Publications

4 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=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4 link	c.457+23879T>G		intron_variant	Intron 3 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.457+23879T>G		intron_variant	Intron 3 of 25	1	NM_130797.4	ENSP00000367001.3		P42658-1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33828

AN:

151984

Hom.:

4218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.207

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

GnomAD4 genome

AF:

0.223

AC:

33897

AN:

152102

Hom.:

4236

Cov.:

AF XY:

0.223

AC XY:

16603

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.320

AC:

13256

AN:

41470

American (AMR)

AF:

0.203

AC:

3097

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

353

AN:

3470

East Asian (EAS)

AF:

0.385

AC:

1981

AN:

5148

South Asian (SAS)

AF:

0.210

AC:

1010

AN:

4816

European-Finnish (FIN)

AF:

0.187

AC:

1976

AN:

10588

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11466

AN:

68014

Other (OTH)

AF:

0.207

AC:

439

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1326

2652

3978

5304

6630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.185

Hom.:

12906

Bravo

AF:

0.229

Asia WGS

AF:

0.303

AC:

1052

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

1.2

(source)

DANN

Benign

0.52

PhyloP100

-0.32

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