Variant rs3734016 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000443439.7(ERAP1):c.166G>A(p.Glu56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 1,614,084 control chromosomes in the GnomAD database, including 3,224 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.059 ( 360 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2864 hom. )

Consequence

ERAP1
ENST00000443439.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0240

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018523037).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	NM_001040458.3 linkuse as main transcript	c.166G>A	p.Glu56Lys	missense_variant	2/19	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7 linkuse as main transcript	c.166G>A	p.Glu56Lys	missense_variant	2/19	1	NM_001040458.3	ENSP00000406304	P1	Q9NZ08-1
	ENST00000667085.1 linkuse as main transcript	n.74C>T		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.0588

AC:

8940

AN:

152088

Hom.:

356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0656

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0775

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.0574

Gnomad FIN

AF:

0.0975

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.0426

GnomAD3 exomes

AF:

0.0706

AC:

17749

AN:

251488

Hom.:

958

AF XY:

0.0650

AC XY:

8828

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0672

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.0261

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.0964

Gnomad NFE exome

AF:

0.0394

Gnomad OTH exome

AF:

0.0585

GnomAD4 exome

AF:

0.0525

AC:

76685

AN:

1461878

Hom.:

2864

Cov.:

AF XY:

0.0515

AC XY:

37439

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0622

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.0254

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.0498

Gnomad4 FIN exome

AF:

0.0964

Gnomad4 NFE exome

AF:

0.0431

Gnomad4 OTH exome

AF:

0.0507

GnomAD4 genome

AF:

0.0588

AC:

8948

AN:

152206

Hom.:

360

Cov.:

AF XY:

0.0621

AC XY:

4619

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0655

Gnomad4 AMR

AF:

0.0779

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.0568

Gnomad4 FIN

AF:

0.0975

Gnomad4 NFE

AF:

0.0398

Gnomad4 OTH

AF:

0.0422

Alfa

AF:

0.0428

Hom.:

437

Bravo

AF:

0.0588

TwinsUK

AF:

0.0507

AC:

188

ALSPAC

AF:

0.0420

AC:

162

ESP6500AA

AF:

0.0588

AC:

259

ESP6500EA

AF:

0.0398

AC:

342

ExAC

AF:

0.0664

AC:

8061

Asia WGS

AF:

0.116

AC:

404

AN:

3478

EpiCase

AF:

0.0365

EpiControl

AF:

0.0346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0083

.;T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.13

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.54

N;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.050

N;N;N

REVEL

Benign

0.043

Sift

Benign

0.71

T;T;T

Sift4G

Benign

0.91

T;T;T

Polyphen

0.0080

B;B;.

Vest4

0.083

MPC

0.083

ClinPred

0.0023

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.086

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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