19-4688818-G-T

Variant names:

• chr19-4688818-G-T
• rs187026346
• NM_139159.5:c.1824C>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_139159.5(DPP9):​c.1824C>A​(p.Gly608Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000832 in 1,496,834 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00077 (15 hom.)
• Consequence: DPP9 NM_139159.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05
• Publications: 1 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-AS1 (HGNC:50706): (DPP9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-4688818-G-T is Benign according to our data. Variant chr19-4688818-G-T is described in ClinVar as Benign. ClinVar VariationId is 713315.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.05 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00137 (209/152380) while in subpopulation EAS AF = 0.038 (197/5190). AF 95% confidence interval is 0.0336. There are 4 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139159.5. 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
	DPP9	NM_139159.5	MANE Select	c.1824C>A	p.Gly608Gly	synonymous	Exon 16 of 22	NP_631898.3
	DPP9	NM_001384611.1		c.1824C>A	p.Gly608Gly	synonymous	Exon 15 of 21	NP_001371540.1	Q86TI2-2
	DPP9	NM_001384612.1		c.1824C>A	p.Gly608Gly	synonymous	Exon 17 of 23	NP_001371541.1	Q86TI2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP9	ENST00000262960.14	TSL:1 MANE Select	c.1824C>A	p.Gly608Gly	synonymous	Exon 16 of 22	ENSP00000262960.8	Q86TI2-2
	DPP9	ENST00000600621.6	TSL:4	c.1824C>A	p.Gly608Gly	synonymous	Exon 16 of 22	ENSP00000472549.2	Q86TI2-2
	DPP9	ENST00000601130.6	TSL:4	c.1824C>A	p.Gly608Gly	synonymous	Exon 17 of 23	ENSP00000471629.2	Q86TI2-2

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 208 AN: 152262 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00203 AC: 306 AN: 150764 AF XY: 0.00174

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0386

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000646

Gnomad OTH exome AF: 0.000336

GnomAD4 exome AF: 0.000771 AC: 1036 AN: 1344454 Hom.: 15 Cov.: 31 AF XY: 0.000735 AC XY: 488 AN XY: 663970

African (AFR) AF: 0.00 AC: 0 AN: 26242

American (AMR) AF: 0.0000995 AC: 2 AN: 20100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22330

East Asian (EAS) AF: 0.0281 AC: 890 AN: 31624

South Asian (SAS) AF: 0.000469 AC: 32 AN: 68174

European-Finnish (FIN) AF: 0.0000202 AC: 1 AN: 49584

Middle Eastern (MID) AF: 0.000184 AC: 1 AN: 5422

European-Non Finnish (NFE) AF: 0.0000619 AC: 66 AN: 1065580

Other (OTH) AF: 0.000794 AC: 44 AN: 55398

GnomAD4 genome AF: 0.00137 AC: 209 AN: 152380 Hom.: 4 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74518

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0380 AC: 197 AN: 5190

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.00160

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.7
DANN	Benign	0.85
PhyloP100		1.0
PromoterAI		0.0054	Neutral
Mutation Taster		=100/0	polymorphism

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: rs187026346; hg19: chr19-4688830;