7-154860569-C-T

Variant names:

• chr7-154860569-C-T
• rs878742
• NM_130797.4:c.1714+6742C>T

Variant summary

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

The NM_130797.4(DPP6):​c.1714+6742C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,184 control chromosomes in the GnomAD database, including 2,181 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 0.15 (2181 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 2 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

DPP6-AS1 (HGNC:40194):

LOC105375580 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	NM_130797.4	MANE Select	c.1714+6742C>T		intron	N/A	NP_570629.2	P42658-1
	DPP6	NM_001364497.2		c.1531+6742C>T		intron	N/A	NP_001351426.1	A0A994J7K0
	DPP6	NM_001364498.2		c.1531+6742C>T		intron	N/A	NP_001351427.1	A0A994J7K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.1714+6742C>T		intron	N/A	ENSP00000367001.3	P42658-1
	DPP6	ENST00000332007.7	TSL:1	c.1528+6742C>T		intron	N/A	ENSP00000328226.3	P42658-2
	DPP6	ENST00000404039.5	TSL:1	c.1522+6742C>T		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23414 AN: 152066 Hom.: 2178 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.154 AC: 23425 AN: 152184 Hom.: 2181 Cov.: 33 AF XY: 0.159 AC XY: 11826 AN XY: 74404

African (AFR) AF: 0.151 AC: 6264 AN: 41520

American (AMR) AF: 0.226 AC: 3463 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2378 AN: 5168

South Asian (SAS) AF: 0.176 AC: 850 AN: 4834

European-Finnish (FIN) AF: 0.143 AC: 1510 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8146 AN: 67980

Other (OTH) AF: 0.152 AC: 322 AN: 2114

Alfa AF: 0.130 Hom.: 1948

Bravo AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.28
DANN	Benign	0.37
PhyloP100		-2.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs878742;

hg19: chr7-154652279;