chr2-162044379-C-T

Variant names:

• chr2-162044379-C-T
• rs3788979
• NM_001935.4:c.366+1153G>A

Variant summary

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

The NM_001935.4(DPP4):​c.366+1153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,674 control chromosomes in the GnomAD database, including 2,117 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 0.15 (2117 hom., cov: 31)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.899
• Publications: 33 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP4	NM_001935.4	c.366+1153G>A		intron_variant	Intron 5 of 25	ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.366+1153G>A		intron_variant	Intron 5 of 25	1	NM_001935.4	ENSP00000353731.3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22064 AN: 151556 Hom.: 2120 Cov.: 31

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.146 AC: 22072 AN: 151674 Hom.: 2117 Cov.: 31 AF XY: 0.149 AC XY: 11069 AN XY: 74074

African (AFR) AF: 0.0894 AC: 3695 AN: 41350

American (AMR) AF: 0.181 AC: 2758 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2635 AN: 5130

South Asian (SAS) AF: 0.145 AC: 695 AN: 4784

European-Finnish (FIN) AF: 0.203 AC: 2137 AN: 10506

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9353 AN: 67892

Other (OTH) AF: 0.124 AC: 260 AN: 2102

Alfa AF: 0.130 Hom.: 1491

Bravo AF: 0.145

Asia WGS AF: 0.283 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	20
DANN	Benign	0.79
PhyloP100		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3788979; hg19: chr2-162900889;