Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001040458.3(ERAP1):c.1037G>A(p.Gly346Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 1,613,580 control chromosomes in the GnomAD database, including 5,177 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.097 ( 1002 hom., cov: 31)

Exomes 𝑓: 0.069 ( 4175 hom. )

Consequence

ERAP1
NM_001040458.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.526

Publications

35 publications found

Variant links:

Genes affected

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020050406).

BP6

Variant 5-96793840-C-T is Benign according to our data. Variant chr5-96793840-C-T is described in ClinVar as Benign. ClinVar VariationId is 1280185.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ERAP1	NM_001040458.3	MANE Select	c.1037G>A	p.Gly346Asp	missense	Exon 6 of 19	NP_001035548.1
ERAP1	NM_001349244.2		c.1037G>A	p.Gly346Asp	missense	Exon 6 of 20	NP_001336173.1
ERAP1	NM_016442.5		c.1037G>A	p.Gly346Asp	missense	Exon 6 of 20	NP_057526.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.1037G>A	p.Gly346Asp	missense	Exon 6 of 19	ENSP00000406304.2
ERAP1	ENST00000296754.7	TSL:1	c.1037G>A	p.Gly346Asp	missense	Exon 6 of 20	ENSP00000296754.3
ERAP1	ENST00000503311.1	TSL:4	n.-169G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0968

AC:

14729

AN:

152112

Hom.:

999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0548

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0349

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0653

Gnomad OTH

AF:

0.0732

GnomAD2 exomes

AF:

0.0692

AC:

17384

AN:

251186

AF XY:

0.0711

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0375

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.0352

Gnomad NFE exome

AF:

0.0650

Gnomad OTH exome

AF:

0.0579

GnomAD4 exome

AF:

0.0694

AC:

101464

AN:

1461350

Hom.:

4175

Cov.:

AF XY:

0.0707

AC XY:

51414

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.197

AC:

6584

AN:

33452

American (AMR)

AF:

0.0398

AC:

1781

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0985

AC:

2573

AN:

26128

East Asian (EAS)

AF:

0.000479

AC:

AN:

39698

South Asian (SAS)

AF:

0.112

AC:

9650

AN:

86244

European-Finnish (FIN)

AF:

0.0359

AC:

1919

AN:

53406

Middle Eastern (MID)

AF:

0.0977

AC:

563

AN:

5764

European-Non Finnish (NFE)

AF:

0.0665

AC:

73865

AN:

1111570

Other (OTH)

AF:

0.0747

AC:

4510

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

4317

8634

12951

17268

21585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2866

5732

8598

11464

14330

<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:

0.0969

AC:

14756

AN:

152230

Hom.:

1002

Cov.:

AF XY:

0.0942

AC XY:

7010

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.192

AC:

7987

AN:

41524

American (AMR)

AF:

0.0547

AC:

836

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

376

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5184

South Asian (SAS)

AF:

0.111

AC:

536

AN:

4822

European-Finnish (FIN)

AF:

0.0349

AC:

370

AN:

10602

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0654

AC:

4448

AN:

68020

Other (OTH)

AF:

0.0724

AC:

153

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

678

1356

2035

2713

3391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.0741

Hom.:

1423

Bravo

AF:

0.101

TwinsUK

AF:

0.0715

AC:

265

ALSPAC

AF:

0.0711

AC:

274

ESP6500AA

AF:

0.186

AC:

820

ESP6500EA

AF:

0.0690

AC:

593

ExAC

AF:

0.0741

AC:

8999

Asia WGS

AF:

0.0490

AC:

172

AN:

3476

EpiCase

AF:

0.0700

EpiControl

AF:

0.0690

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.9

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.068

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.1

PhyloP100

0.53

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.2

REVEL

Benign

0.034

Sift

Benign

0.17

Sift4G

Benign

0.22

Polyphen

0.016

Vest4

0.098

MPC

0.10

ClinPred

0.0065

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.79

Mutation Taster

=80/20

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over