rs17848916

Positions:

• chr2-162047874-A-C

Variant summary

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

The NM_001935.4(DPP4):​c.95-373T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 152,308 control chromosomes in the GnomAD database, including 249 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 0.038 (249 hom., cov: 32)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

Genes affected

DPP4 (HGNC:3009): (dipeptidyl peptidase 4) The DPP4 gene encodes dipeptidyl peptidase 4, which is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26. It is an intrinsic type II transmembrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. Dipeptidyl peptidase 4 is highly involved in glucose and insulin metabolism, as well as in immune regulation. This protein was shown to be a functional receptor for Middle East respiratory syndrome coronavirus (MERS-CoV), and protein modeling suggests that it may play a similar role with SARS-CoV-2, the virus responsible for COVID-19. [provided by RefSeq, Apr 2020]

DPP4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP4	NM_001935.4	c.95-373T>G		intron_variant		ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.95-373T>G		intron_variant		1	NM_001935.4	ENSP00000353731.3

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5770 AN: 152190 Hom.: 246 Cov.: 32

Gnomad AFR AF: 0.0974

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0479

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0307

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

GnomAD4 genome AF: 0.0380 AC: 5788 AN: 152308 Hom.: 249 Cov.: 32 AF XY: 0.0373 AC XY: 2781 AN XY: 74476

Gnomad4 AFR AF: 0.0974

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.0480

Gnomad4 SAS AF: 0.0246

Gnomad4 FIN AF: 0.00480

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0274 Hom.: 14

Bravo AF: 0.0418

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.75

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: rs17848916; hg19: chr2-162904384;