Variant 5-96901622-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_022350.5(ERAP2):c.1689G>A(p.Gln563Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,613,618 control chromosomes in the GnomAD database, including 218,582 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 0.54 ( 22344 hom., cov: 32)

Exomes 𝑓: 0.52 ( 196238 hom. )

Consequence

ERAP2
NM_022350.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=1.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP2	NM_022350.5 link	c.1689G>A	p.Gln563Gln	synonymous_variant	11/19	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.1689G>A	p.Gln563Gln	synonymous_variant	11/19	1	NM_022350.5	ENSP00000400376.3		Q6P179-1

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82250

AN:

151892

Hom.:

22342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.548

AC:

137649

AN:

251092

Hom.:

38048

AF XY:

0.547

AC XY:

74220

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.620

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.588

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.527

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.517

AC:

755105

AN:

1461608

Hom.:

196238

Cov.:

AF XY:

0.518

AC XY:

376823

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.579

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.579

Gnomad4 EAS exome

AF:

0.540

Gnomad4 SAS exome

AF:

0.587

Gnomad4 FIN exome

AF:

0.526

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.541

AC:

82287

AN:

152010

Hom.:

22344

Cov.:

AF XY:

0.544

AC XY:

40382

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.585

Gnomad4 EAS

AF:

0.555

Gnomad4 SAS

AF:

0.580

Gnomad4 FIN

AF:

0.530

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.535

Alfa

AF:

0.528

Hom.:

24875

Bravo

AF:

0.552

Asia WGS

AF:

0.488

AC:

1699

AN:

3478

EpiCase

AF:

0.517

EpiControl

AF:

0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.5

DANN

Benign

0.89

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