rs1611001

Variant names:

• chr7-154612851-ATTGGGCTTATT-A
• rs1611001
• NM_130797.4:c.628-24969_628-24959delTTGGGCTTATT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_130797.4(DPP6):​c.628-24969_628-24959delTTGGGCTTATT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13439 hom., cov: 0)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 6 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.628-24969_628-24959delTTGGGCTTATT		intron_variant	Intron 5 of 25	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.628-24969_628-24959delTTGGGCTTATT		intron_variant	Intron 5 of 25	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61437 AN: 151954 Hom.: 13428 Cov.: 0

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.404 AC: 61475 AN: 152072 Hom.: 13439 Cov.: 0 AF XY: 0.411 AC XY: 30557 AN XY: 74322

African (AFR) AF: 0.228 AC: 9478 AN: 41502

American (AMR) AF: 0.497 AC: 7589 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3468

East Asian (EAS) AF: 0.648 AC: 3342 AN: 5158

South Asian (SAS) AF: 0.558 AC: 2684 AN: 4812

European-Finnish (FIN) AF: 0.478 AC: 5054 AN: 10564

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30161 AN: 67976

Other (OTH) AF: 0.446 AC: 942 AN: 2110

Alfa AF: 0.406 Hom.: 1409

Asia WGS AF: 0.582 AC: 2023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1611001; hg19: chr7-154404561; COSMIC: COSV59650498;