rs732631

Variant names:

• chr19-4719013-C-G
• rs732631
• NM_139159.5:c.56+838G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-4719013-C-G
• chr19-4719013-C-T

Variant summary

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

The NM_139159.5(DPP9):​c.56+838G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,858 control chromosomes in the GnomAD database, including 8,758 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 0.33 (8758 hom., cov: 30)
• Consequence: DPP9 NM_139159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• Publications: 2 publications found

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]

DPP9 Gene-Disease associations (from GenCC):

• hatipoglu immunodeficiency syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP9	NM_139159.5	c.56+838G>C		intron_variant	Intron 3 of 21	ENST00000262960.14	NP_631898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP9	ENST00000262960.14	c.56+838G>C		intron_variant	Intron 3 of 21	1	NM_139159.5	ENSP00000262960.8

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50768 AN: 151740 Hom.: 8752 Cov.: 30

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.335 AC: 50810 AN: 151858 Hom.: 8758 Cov.: 30 AF XY: 0.331 AC XY: 24576 AN XY: 74184

African (AFR) AF: 0.327 AC: 13537 AN: 41388

American (AMR) AF: 0.295 AC: 4497 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3468

East Asian (EAS) AF: 0.136 AC: 701 AN: 5166

South Asian (SAS) AF: 0.214 AC: 1032 AN: 4812

European-Finnish (FIN) AF: 0.380 AC: 4006 AN: 10554

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24807 AN: 67926

Other (OTH) AF: 0.330 AC: 695 AN: 2106

Alfa AF: 0.205 Hom.: 473

Bravo AF: 0.333

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.57
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs732631; hg19: chr19-4719025;