rs7608798

Variant names:

• chr2-162033707-G-A
• rs7608798
• NM_001935.4:c.775-54C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-162033707-G-A
• chr2-162033707-G-C
• chr2-162033707-G-T

Variant summary

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

The NM_001935.4(DPP4):​c.775-54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,202,210 control chromosomes in the GnomAD database, including 70,896 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 0.35 (9399 hom., cov: 26)
  • Exomes 𝑓: 0.33 (61497 hom.)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 25 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001935.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP4	NM_001935.4	MANE Select	c.775-54C>T		intron	N/A	NP_001926.2
	DPP4	NM_001379604.1		c.772-54C>T		intron	N/A	NP_001366533.1
	DPP4	NM_001379605.1		c.769-54C>T		intron	N/A	NP_001366534.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP4	ENST00000360534.8	TSL:1 MANE Select	c.775-54C>T		intron	N/A	ENSP00000353731.3
	DPP4	ENST00000434918.6	TSL:1	n.*263-54C>T		intron	N/A	ENSP00000402259.2
	DPP4	ENST00000461836.6	TSL:1	n.1307-54C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52018 AN: 148930 Hom.: 9399 Cov.: 26

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.327 AC: 344717 AN: 1053198 Hom.: 61497 AF XY: 0.325 AC XY: 174421 AN XY: 536054

African (AFR) AF: 0.346 AC: 8055 AN: 23306

American (AMR) AF: 0.348 AC: 10331 AN: 29660

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 8869 AN: 21360

East Asian (EAS) AF: 0.710 AC: 24719 AN: 34832

South Asian (SAS) AF: 0.243 AC: 16609 AN: 68392

European-Finnish (FIN) AF: 0.401 AC: 17963 AN: 44814

Middle Eastern (MID) AF: 0.300 AC: 1323 AN: 4412

European-Non Finnish (NFE) AF: 0.309 AC: 241282 AN: 780296

Other (OTH) AF: 0.337 AC: 15566 AN: 46126

GnomAD4 genome AF: 0.349 AC: 52023 AN: 149012 Hom.: 9399 Cov.: 26 AF XY: 0.352 AC XY: 25552 AN XY: 72524

African (AFR) AF: 0.349 AC: 14185 AN: 40668

American (AMR) AF: 0.336 AC: 5049 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1423 AN: 3450

East Asian (EAS) AF: 0.646 AC: 3245 AN: 5026

South Asian (SAS) AF: 0.257 AC: 1215 AN: 4730

European-Finnish (FIN) AF: 0.418 AC: 3985 AN: 9526

Middle Eastern (MID) AF: 0.316 AC: 91 AN: 288

European-Non Finnish (NFE) AF: 0.324 AC: 21804 AN: 67340

Other (OTH) AF: 0.322 AC: 664 AN: 2062

Alfa AF: 0.277 Hom.: 1246

Bravo AF: 0.351

Asia WGS AF: 0.399 AC: 1367 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.61
PhyloP100		0.12
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: rs7608798; hg19: chr2-162890217; COSMIC: COSV62108770; COSMIC: COSV62108770;