rs352457

Positions:

• chr15-65484867-G-A

Variant summary

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

The NM_130434.5(DPP8):​c.1017+232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,968 control chromosomes in the GnomAD database, including 1,884 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 0.12 (1884 hom., cov: 31)
• Consequence: DPP8 NM_130434.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP8	NM_130434.5	c.1017+232C>T		intron_variant		ENST00000300141.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP8	ENST00000300141.11	c.1017+232C>T		intron_variant		1	NM_130434.5	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18104 AN: 151850 Hom.: 1880 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.0346

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.119 AC: 18135 AN: 151968 Hom.: 1884 Cov.: 31 AF XY: 0.116 AC XY: 8599 AN XY: 74276

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.0589

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.0459

Gnomad4 SAS AF: 0.0602

Gnomad4 FIN AF: 0.0346

Gnomad4 NFE AF: 0.0574

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0725 Hom.: 305

Bravo AF: 0.128

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	12
DANN	Benign	0.52

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: rs352457; hg19: chr15-65777205;