chr16-89637957-G-C

Position:

• chr16-89637957-G-C

Variant summary

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

The NM_001389466.1(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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E351K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.21 (3890 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44927 hom.)
• Consequence: DPEP1 NM_001389466.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPEP1	NM_001389466.1	c.1051G>C	p.Glu351Gln	missense_variant	10/11	ENST00000690203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPEP1	ENST00000690203.1	c.1051G>C	p.Glu351Gln	missense_variant	10/11		NM_001389466.1	P1

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

GnomAD3 exomes AF: 0.265 AC: 62991 AN: 238124 Hom.: 9225 AF XY: 0.258 AC XY: 33317 AN XY: 129350

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 SAS exome AF: 0.230

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

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.226

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

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.205

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 v4.3

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;T;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;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L;L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.0	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.046	B;B;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1126464; hg19: chr16-89704365; COSMIC: COSV55359253; COSMIC: COSV55359253;