Variant chr5-96903554-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022350.5(ERAP2):c.2006T>A(p.Leu669Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0496 in 1,594,986 control chromosomes in the GnomAD database, including 2,284 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.038 ( 189 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2095 hom. )

Consequence

ERAP2
NM_022350.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.65

Variant links:

Genes affected

ERAP2 (HGNC:29499): (endoplasmic reticulum aminopeptidase 2) This gene encodes a zinc metalloaminopeptidase of the M1 protease family that resides in the endoplasmic reticulum and functions in N-terminal trimming antigenic epitopes for presentation by major histocompatibility complex (MHC) class I molecules. Certain mutations in this gene are associated with the inflammatory arthritis syndrome ankylosing spondylitis and pre-eclampsia. This gene is located adjacent to a closely related aminopeptidase gene on chromosome 5. [provided by RefSeq, Jul 2016]

ERAP2 links:

ERAP1 (HGNC:18173): (endoplasmic reticulum aminopeptidase 1) The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

ERAP1 links:

ENSG00000247121 (HGNC:):

ENSG00000247121 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039714277).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP2	NM_022350.5 link	c.2006T>A	p.Leu669Gln	missense_variant	13/19	ENST00000437043.8	NP_071745.1	Q6P179-1B2R769

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8 link	c.2006T>A	p.Leu669Gln	missense_variant	13/19	1	NM_022350.5	ENSP00000400376.3		Q6P179-1

Frequencies

GnomAD3 genomes

AF:

0.0380

AC:

5786

AN:

152174

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00994

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.0466

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0194

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0558

Gnomad OTH

AF:

0.0598

GnomAD3 exomes

AF:

0.0403

AC:

9445

AN:

234360

Hom.:

265

AF XY:

0.0421

AC XY:

5325

AN XY:

126564

show subpopulations

Gnomad AFR exome

AF:

0.00834

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0735

Gnomad EAS exome

AF:

0.000560

Gnomad SAS exome

AF:

0.0318

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.0561

Gnomad OTH exome

AF:

0.0514

GnomAD4 exome

AF:

0.0509

AC:

73388

AN:

1442694

Hom.:

2095

Cov.:

AF XY:

0.0509

AC XY:

36441

AN XY:

716500

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.0361

Gnomad4 ASJ exome

AF:

0.0688

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.0315

Gnomad4 FIN exome

AF:

0.0211

Gnomad4 NFE exome

AF:

0.0565

Gnomad4 OTH exome

AF:

0.0526

GnomAD4 genome

AF:

0.0380

AC:

5782

AN:

152292

Hom.:

189

Cov.:

AF XY:

0.0362

AC XY:

2694

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00991

Gnomad4 AMR

AF:

0.0466

Gnomad4 ASJ

AF:

0.0703

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0288

Gnomad4 FIN

AF:

0.0194

Gnomad4 NFE

AF:

0.0559

Gnomad4 OTH

AF:

0.0596

Alfa

AF:

0.0535

Hom.:

197

Bravo

AF:

0.0396

TwinsUK

AF:

0.0577

AC:

214

ALSPAC

AF:

0.0524

AC:

202

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.0569

AC:

489

ExAC

AF:

0.0397

AC:

4823

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D;D

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.0

M;.;.

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.1

D;D;D

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.60

MPC

0.33

ClinPred

0.028

GERP RS

2.4

Varity_R

0.96

gMVP

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over