15-65513051-T-C

Variant names:

• chr15-65513051-T-C
• rs352476
• NM_130434.5:c.-11-487A>G

Variant summary

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

The NM_130434.5(DPP8):​c.-11-487A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,112 control chromosomes in the GnomAD database, including 17,252 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 0.44 (17252 hom., cov: 32)
• Consequence: DPP8 NM_130434.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 11 publications found

Genes affected

DPP8 (HGNC:16490): (dipeptidyl peptidase 8) This gene encodes a member of the peptidase S9B family, a small family of dipeptidyl peptidases that are able to cleave peptide substrates at a prolyl bond. The encoded protein shares similarity with dipeptidyl peptidase IV in that it is ubiquitously expressed, and hydrolyzes the same substrates. These similarities suggest that, like dipeptidyl peptidase IV, this protein may play a role in T-cell activation and immune function. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP8	NM_130434.5	c.-11-487A>G		intron_variant	Intron 1 of 19	ENST00000300141.11	NP_569118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP8	ENST00000300141.11	c.-11-487A>G		intron_variant	Intron 1 of 19	1	NM_130434.5	ENSP00000300141.6

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66924 AN: 151994 Hom.: 17255 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.440 AC: 66940 AN: 152112 Hom.: 17252 Cov.: 32 AF XY: 0.441 AC XY: 32765 AN XY: 74348

African (AFR) AF: 0.170 AC: 7044 AN: 41534

American (AMR) AF: 0.564 AC: 8622 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3468

East Asian (EAS) AF: 0.211 AC: 1090 AN: 5168

South Asian (SAS) AF: 0.426 AC: 2055 AN: 4828

European-Finnish (FIN) AF: 0.536 AC: 5650 AN: 10550

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38801 AN: 67970

Other (OTH) AF: 0.461 AC: 972 AN: 2108

Alfa AF: 0.524 Hom.: 50557

Bravo AF: 0.429

Asia WGS AF: 0.338 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.64
PhyloP100		1.0
PromoterAI		0.086	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs352476; hg19: chr15-65805389;