rs1047053

Variant names:

• chr7-154893261-G-A
• rs1047053
• NM_130797.4:c.*781G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-154893261-G-A
• chr7-154893261-G-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.*781G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 252,728 control chromosomes in the GnomAD database, including 85,567 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 0.84 (54228 hom., cov: 27)
  • Exomes 𝑓: 0.78 (31339 hom.)
• Consequence: DPP6 NM_130797.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 7 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.*781G>A		3_prime_UTR_variant	Exon 26 of 26	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.*781G>A		3_prime_UTR_variant	Exon 26 of 26	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.843 AC: 127658 AN: 151520 Hom.: 54167 Cov.: 27

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.821

GnomAD4 exome AF: 0.783 AC: 79186 AN: 101092 Hom.: 31339 Cov.: 0 AF XY: 0.779 AC XY: 42357 AN XY: 54388

African (AFR) AF: 0.955 AC: 2293 AN: 2400

American (AMR) AF: 0.854 AC: 3631 AN: 4254

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 1972 AN: 2450

East Asian (EAS) AF: 0.702 AC: 2430 AN: 3464

South Asian (SAS) AF: 0.746 AC: 14162 AN: 18980

European-Finnish (FIN) AF: 0.846 AC: 3993 AN: 4722

Middle Eastern (MID) AF: 0.781 AC: 275 AN: 352

European-Non Finnish (NFE) AF: 0.781 AC: 46363 AN: 59344

Other (OTH) AF: 0.793 AC: 4067 AN: 5126

GnomAD4 genome AF: 0.843 AC: 127779 AN: 151636 Hom.: 54228 Cov.: 27 AF XY: 0.843 AC XY: 62449 AN XY: 74064

African (AFR) AF: 0.955 AC: 39468 AN: 41322

American (AMR) AF: 0.833 AC: 12694 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2822 AN: 3468

East Asian (EAS) AF: 0.716 AC: 3654 AN: 5106

South Asian (SAS) AF: 0.761 AC: 3648 AN: 4792

European-Finnish (FIN) AF: 0.855 AC: 8993 AN: 10520

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53784 AN: 67884

Other (OTH) AF: 0.822 AC: 1731 AN: 2106

Alfa AF: 0.806 Hom.: 78387

Bravo AF: 0.846

Asia WGS AF: 0.791 AC: 2751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		0.33

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: rs1047053; hg19: chr7-154684971;