chr5-96886775-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022350.5(ERAP2):c.835T>G(p.Ser279Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,505,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

ERAP2
NM_022350.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.189

Publications

3 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:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039256275).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022350.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERAP2	NM_022350.5	MANE Select	c.835T>G	p.Ser279Ala	missense	Exon 4 of 19	NP_071745.1	Q6P179-1
ERAP2	NM_001130140.3		c.835T>G	p.Ser279Ala	missense	Exon 4 of 19	NP_001123612.1
ERAP2	NM_001437802.1		c.835T>G	p.Ser279Ala	missense	Exon 4 of 18	NP_001424731.1	A0AAQ5BHS6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERAP2	ENST00000437043.8	TSL:1 MANE Select	c.835T>G	p.Ser279Ala	missense	Exon 4 of 19	ENSP00000400376.3	Q6P179-1
ERAP2	ENST00000510309.1	TSL:1	c.835T>G	p.Ser279Ala	missense	Exon 3 of 4	ENSP00000425758.1	Q6P179-4
ERAP2	ENST00000379904.8	TSL:1	c.715-2410T>G		intron	N/A	ENSP00000369235.4	Q6P179-3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000803

AC:

AN:

236626

AF XY:

0.000101

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000163

AC:

220

AN:

1353390

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

103

AN XY:

665684

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31716

American (AMR)

AF:

0.00

AC:

AN:

41252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23756

East Asian (EAS)

AF:

0.00

AC:

AN:

37320

South Asian (SAS)

AF:

0.00

AC:

AN:

70734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5356

European-Non Finnish (NFE)

AF:

0.000192

AC:

200

AN:

1039568

Other (OTH)

AF:

0.000347

AC:

AN:

54802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000723

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000117

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.9

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.011

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.41

M_CAP

Benign

0.0081

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.66

PhyloP100

-0.19

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.0

REVEL

Benign

0.030

Sift

Benign

0.62

Sift4G

Benign

0.36

Polyphen

0.025

Vest4

0.23

MVP

0.092

MPC

0.048

ClinPred

0.035

GERP RS

2.3

Varity_R

0.31

gMVP

0.12

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over