rs758316

Variant names:

• chr7-153934563-G-A
• rs758316
• ENST00000404039.5:c.51+46829G>A

Variant summary

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

The ENST00000404039.5(DPP6):​c.51+46829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,974 control chromosomes in the GnomAD database, including 31,051 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 0.63 (31051 hom., cov: 31)
• Consequence: DPP6 ENST00000404039.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_001364497.2	c.60+185555G>A		intron_variant	Intron 2 of 26		NP_001351426.1
DPP6	NM_001364498.2	c.60+185555G>A		intron_variant	Intron 2 of 26		NP_001351427.1
DPP6	NM_001364499.2	c.60+185555G>A		intron_variant	Intron 2 of 26		NP_001351428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000404039.5	c.51+46829G>A		intron_variant	Intron 1 of 25	1		ENSP00000385578.1
DPP6	ENST00000706130.1	c.60+185555G>A		intron_variant	Intron 2 of 26			ENSP00000516215.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96219 AN: 151856 Hom.: 31032 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.634 AC: 96282 AN: 151974 Hom.: 31051 Cov.: 31 AF XY: 0.625 AC XY: 46386 AN XY: 74256

African (AFR) AF: 0.761 AC: 31534 AN: 41462

American (AMR) AF: 0.603 AC: 9202 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1911 AN: 3472

East Asian (EAS) AF: 0.400 AC: 2066 AN: 5160

South Asian (SAS) AF: 0.497 AC: 2389 AN: 4808

European-Finnish (FIN) AF: 0.521 AC: 5496 AN: 10552

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.612 AC: 41556 AN: 67938

Other (OTH) AF: 0.630 AC: 1331 AN: 2112

Alfa AF: 0.615 Hom.: 123602

Bravo AF: 0.645

Asia WGS AF: 0.464 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.19
DANN	Benign	0.48
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs758316; hg19: chr7-153631648;