dbSNP rs2287988: ERAP2:p.Gln563Gln (chr5-96901622-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

48 publications found

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:

ENSG00000247121 (HGNC:):

ENSG00000247121 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ERAP2	NM_022350.5 link	c.1689G>A	p.Gln563Gln	synonymous_variant	Exon 11 of 19	ENST00000437043.8	NP_071745.1	Q6P179-1B2R769

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8 link	c.1689G>A	p.Gln563Gln	synonymous_variant	Exon 11 of 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

GnomAD2 exomes

AF:

0.548

AC:

137649

AN:

251092

AF XY:

0.547

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 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

African (AFR)

AF:

0.579

AC:

19387

AN:

33470

American (AMR)

AF:

0.618

AC:

27620

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

15130

AN:

26130

East Asian (EAS)

AF:

0.540

AC:

21443

AN:

39688

South Asian (SAS)

AF:

0.587

AC:

50595

AN:

86242

European-Finnish (FIN)

AF:

0.526

AC:

28071

AN:

53416

Middle Eastern (MID)

AF:

0.611

AC:

3522

AN:

5764

European-Non Finnish (NFE)

AF:

0.502

AC:

557982

AN:

1111820

Other (OTH)

AF:

0.519

AC:

31355

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

19913

39825

59738

79650

99563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16372

32744

49116

65488

81860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.541

AC:

82287

AN:

152010

Hom.:

22344

Cov.:

AF XY:

0.544

AC XY:

40382

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.571

AC:

23685

AN:

41460

American (AMR)

AF:

0.586

AC:

8940

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

2026

AN:

3466

East Asian (EAS)

AF:

0.555

AC:

2866

AN:

5164

South Asian (SAS)

AF:

0.580

AC:

2791

AN:

4816

European-Finnish (FIN)

AF:

0.530

AC:

5595

AN:

10548

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.510

AC:

34646

AN:

67976

Other (OTH)

AF:

0.535

AC:

1128

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1980

3960

5940

7920

9900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.531

Hom.:

31742

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

(source)

DANN

Benign

0.89

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over