rs878742

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-154860569-C-G
• chr7-154860569-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_130797.4(DPP6):​c.1714+6742C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 152,202 control chromosomes in the GnomAD database, including 3 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 0.00022 (3 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

ENSG00000236408 (HGNC:40194):

LOC105375580 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS2: High AC in GnomAd4 at 34 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.1714+6742C>G		intron_variant	Intron 17 of 25	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.1714+6742C>G		intron_variant	Intron 17 of 25	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 34 AN: 152084 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

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

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152202 Hom.: 3 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74418

African (AFR) AF: 0.000169 AC: 7 AN: 41526

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67986

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00000533 Hom.: 1948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.38
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

Other links and lift over

dbSNP: rs878742; hg19: chr7-154652279;