dbSNP rs1230358: ERAP2:n.54T>G (chr5-96876037-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NR_137637.2(ERAP2):n.54T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,154 control chromosomes in the GnomAD database, including 31,369 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 0.64 ( 31311 hom., cov: 30)

Exomes 𝑓: 0.62 ( 58 hom. )

Consequence

ERAP2
NR_137637.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.278

Publications

24 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
ERAP2	NR_137637.2 link	n.54T>G	non_coding_transcript_exon_variant	Exon 1 of 19
ERAP2	NM_001130140.3 link	c.-176T>G	5_prime_UTR_variant	Exon 1 of 19	NP_001123612.1	Q6P179-1B2R769
ERAP2	NM_001437802.1 link	c.-613T>G	5_prime_UTR_variant	Exon 1 of 18	NP_001424731.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ERAP2	ENST00000510373.6 link	c.-176T>G	5_prime_UTR_variant	Exon 1 of 19	2	ENSP00000421175.2	D6RGW0
ENSG00000247121	ENST00000501338.6 link	n.1689-2659A>C	intron_variant	Intron 1 of 3	2
ENSG00000247121	ENST00000655392.1 link	n.819-2365A>C	intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.639

AC:

96907

AN:

151748

Hom.:

31287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.722

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.696

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.638

GnomAD4 exome

AF:

0.622

AC:

179

AN:

288

Hom.:

Cov.:

AF XY:

0.641

AC XY:

AN XY:

142

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.551

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.691

AC:

AN:

110

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.656

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.639

AC:

96973

AN:

151866

Hom.:

31311

Cov.:

AF XY:

0.643

AC XY:

47696

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.721

AC:

29891

AN:

41434

American (AMR)

AF:

0.671

AC:

10238

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.696

AC:

2411

AN:

3466

East Asian (EAS)

AF:

0.669

AC:

3447

AN:

5156

South Asian (SAS)

AF:

0.724

AC:

3473

AN:

4800

European-Finnish (FIN)

AF:

0.631

AC:

6637

AN:

10526

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.571

AC:

38792

AN:

67920

Other (OTH)

AF:

0.633

AC:

1329

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1777

3554

5332

7109

8886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<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:

0.655

Hom.:

10374

Bravo

AF:

0.650

Asia WGS

AF:

0.650

AC:

2260

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.2

(source)

DANN

Benign

0.36

PhyloP100

-0.28

PromoterAI

-0.010

Neutral

(source)

Mutation Taster

=300/0

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