16-89637957-G-C

Variant names:

• chr16-89637957-G-C
• rs1126464
• NM_001389466.1:c.1051G>C

Variant summary

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

The NM_004413.4(DPEP1):​c.1051G>C​(p.Glu351Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,607,234 control chromosomes in the GnomAD database, including 48,817 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3890 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44927 hom.)
• Consequence: DPEP1 NM_004413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 66 publications found

Genes affected

DPEP1 (HGNC:3002): (dipeptidase 1) The protein encoded by this gene is a kidney membrane enzyme involved in the metabolism of glutathione and other similar proteins by dipeptide hydrolysis. The encoded protein is known to regulate leukotriene activity by catalyzing the conversion of leukotriene D4 to leukotriene E4. This protein uses zinc as a cofactor and acts as a disulfide-linked homodimer. [provided by RefSeq, Dec 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.002023369).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004413.4. 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
	DPEP1	NM_001389466.1	MANE Select	c.1051G>C	p.Glu351Gln	missense	Exon 10 of 11	NP_001376395.1
	DPEP1	NM_001128141.3		c.1051G>C	p.Glu351Gln	missense	Exon 10 of 11	NP_001121613.1
	DPEP1	NM_001389467.1		c.1051G>C	p.Glu351Gln	missense	Exon 10 of 11	NP_001376396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPEP1	ENST00000690203.1	MANE Select	c.1051G>C	p.Glu351Gln	missense	Exon 10 of 11	ENSP00000508584.1
	DPEP1	ENST00000261615.5	TSL:1	c.1051G>C	p.Glu351Gln	missense	Exon 9 of 10	ENSP00000261615.4
	DPEP1	ENST00000393092.7	TSL:1	c.1051G>C	p.Glu351Gln	missense	Exon 10 of 11	ENSP00000376807.3

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32318 AN: 151920 Hom.: 3882 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.203

GnomAD2 exomes AF: 0.265 AC: 62991 AN: 238124 AF XY: 0.258

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.343

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.243 AC: 353823 AN: 1455196 Hom.: 44927 Cov.: 37 AF XY: 0.242 AC XY: 175133 AN XY: 723578

African (AFR) AF: 0.106 AC: 3529 AN: 33398

American (AMR) AF: 0.408 AC: 17752 AN: 43460

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4849 AN: 25992

East Asian (EAS) AF: 0.334 AC: 13169 AN: 39482

South Asian (SAS) AF: 0.232 AC: 19842 AN: 85686

European-Finnish (FIN) AF: 0.310 AC: 16057 AN: 51836

Middle Eastern (MID) AF: 0.155 AC: 892 AN: 5758

European-Non Finnish (NFE) AF: 0.238 AC: 264161 AN: 1109430

Other (OTH) AF: 0.226 AC: 13572 AN: 60154

GnomAD4 genome AF: 0.213 AC: 32332 AN: 152038 Hom.: 3890 Cov.: 32 AF XY: 0.220 AC XY: 16347 AN XY: 74298

African (AFR) AF: 0.114 AC: 4749 AN: 41482

American (AMR) AF: 0.290 AC: 4432 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1767 AN: 5156

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4826

European-Finnish (FIN) AF: 0.305 AC: 3229 AN: 10580

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15757 AN: 67936

Other (OTH) AF: 0.205 AC: 433 AN: 2112

Alfa AF: 0.191 Hom.: 1085

Bravo AF: 0.209

TwinsUK AF: 0.242 AC: 899

ALSPAC AF: 0.241 AC: 928

ESP6500AA AF: 0.110 AC: 481

ESP6500EA AF: 0.227 AC: 1945

ExAC AF: 0.249 AC: 30045

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.5
DANN	Benign	0.77
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.0010
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.021
Sift	Benign	0.26	T
Sift4G	Benign	0.29	T
Polyphen		0.046	B
Vest4		0.081
MPC		0.019
ClinPred		0.0039	T
GERP RS		-5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.68
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1126464; hg19: chr16-89704365; COSMIC: COSV55359253; COSMIC: COSV55359253;