19-4714032-T-C

Position:

• chr19-4714032-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139159.5(DPP9):​c.313+49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,548,806 control chromosomes in the GnomAD database, including 73,314 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 0.40 (15029 hom., cov: 32)
  • Exomes 𝑓: 0.27 (58285 hom.)
• Consequence: DPP9 NM_139159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

Genes affected

DPP9 (HGNC:18648): (dipeptidyl peptidase 9) This gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. The protein has been shown to have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Although the activity of this protein is similar to that of dipeptidyl peptidase 4 (DPP4), it does not appear to be membrane bound. In general, dipeptidyl peptidases appear to be involved in the regulation of the activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. Several transcript variants of this gene have been described but not fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP9	NM_139159.5	c.313+49A>G		intron_variant		ENST00000262960.14	NP_631898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP9	ENST00000262960.14	c.313+49A>G		intron_variant		1	NM_139159.5	ENSP00000262960	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60227 AN: 151912 Hom.: 14983 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.382

GnomAD3 exomes AF: 0.334 AC: 60724 AN: 181618 Hom.: 11687 AF XY: 0.326 AC XY: 31742 AN XY: 97384

Gnomad AFR exome AF: 0.712

Gnomad AMR exome AF: 0.461

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.309

Gnomad SAS exome AF: 0.396

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.275 AC: 383668 AN: 1396776 Hom.: 58285 Cov.: 34 AF XY: 0.276 AC XY: 190027 AN XY: 688182

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.397 AC: 60336 AN: 152030 Hom.: 15029 Cov.: 32 AF XY: 0.396 AC XY: 29444 AN XY: 74326

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.381

Alfa AF: 0.282 Hom.: 7009

Bravo AF: 0.420

Asia WGS AF: 0.402 AC: 1400 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	0.55
DANN	Benign	0.74
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277733; hg19: chr19-4714044; COSMIC: COSV53594632; COSMIC: COSV53594632;