7-153855979-A-T

Variant names:

• chr7-153855979-A-T
• rs6947495
• NM_001364497.2:c.60+106971A>T

Variant summary

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

The NM_001364497.2(DPP6):​c.60+106971A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,144 control chromosomes in the GnomAD database, including 2,779 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 0.19 (2779 hom., cov: 32)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• 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
• ventricular fibrillation, paroxysmal familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal dominant 33

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

LOC107986722 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364497.2. 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_001364497.2		c.60+106971A>T		intron	N/A	NP_001351426.1	A0A994J7K0
	DPP6	NM_001364498.2		c.60+106971A>T		intron	N/A	NP_001351427.1	A0A994J7K0
	DPP6	NM_001364499.2		c.60+106971A>T		intron	N/A	NP_001351428.1	A0A994J7K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000706130.1		c.60+106971A>T		intron	N/A	ENSP00000516215.1	A0A994J7K0

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28613 AN: 152026 Hom.: 2779 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.188 AC: 28628 AN: 152144 Hom.: 2779 Cov.: 32 AF XY: 0.184 AC XY: 13725 AN XY: 74408

African (AFR) AF: 0.156 AC: 6479 AN: 41522

American (AMR) AF: 0.169 AC: 2588 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3472

East Asian (EAS) AF: 0.178 AC: 919 AN: 5170

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1227 AN: 10600

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14591 AN: 67964

Other (OTH) AF: 0.198 AC: 419 AN: 2112

Alfa AF: 0.0659 Hom.: 101

Bravo AF: 0.189

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.63
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs6947495; hg19: chr7-153553064;