rs11670570

Positions:

• chr19-4674787-A-G

Variant summary

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

The ENST00000646573.2(DPP9):​c.*2155T>C variant causes a 3 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,324 control chromosomes in the GnomAD database, including 6,480 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 0.27 (6480 hom., cov: 30)
• Consequence: DPP9 ENST00000646573.2 3_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP9	ENST00000646573.2	c.*2155T>C		3_prime_UTR_variant, NMD_transcript_variant	21/21

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41476 AN: 151204 Hom.: 6465 Cov.: 30

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.274 AC: 41534 AN: 151324 Hom.: 6480 Cov.: 30 AF XY: 0.272 AC XY: 20105 AN XY: 73924

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.294

Alfa AF: 0.233 Hom.: 5721

Bravo AF: 0.288

Asia WGS AF: 0.225 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11670570; hg19: chr19-4674799;