Variant 5-96793832-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001040458.3(ERAP1):c.1045A>G(p.Met349Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,612,274 control chromosomes in the GnomAD database, including 33,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2276 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30940 hom. )

Consequence

ERAP1
NM_001040458.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.70

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017139018).

BP6

Variant 5-96793832-T-C is Benign according to our data. Variant chr5-96793832-T-C is described in ClinVar as [Benign]. Clinvar id is 2688496.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 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.1045A>G	p.Met349Val	missense_variant	6/19	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.1045A>G	p.Met349Val	missense_variant	6/19	1	NM_001040458.3	ENSP00000406304	P1	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.1045A>G	p.Met349Val	missense_variant	6/20	1		ENSP00000296754		Q9NZ08-2

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24678

AN:

152128

Hom.:

2274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0975

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.0469

Gnomad SAS

AF:

0.0909

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.154

AC:

38690

AN:

250984

Hom.:

3577

AF XY:

0.156

AC XY:

21126

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0959

Gnomad AMR exome

AF:

0.0894

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.0498

Gnomad SAS exome

AF:

0.0965

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.198

AC:

288576

AN:

1460028

Hom.:

30940

Cov.:

AF XY:

0.195

AC XY:

141730

AN XY:

726424

show subpopulations

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.0931

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.0452

Gnomad4 SAS exome

AF:

0.0974

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.162

AC:

24695

AN:

152246

Hom.:

2276

Cov.:

AF XY:

0.160

AC XY:

11899

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0974

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.0472

Gnomad4 SAS

AF:

0.0918

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.193

Hom.:

6355

Bravo

AF:

0.155

TwinsUK

AF:

0.225

AC:

833

ALSPAC

AF:

0.227

AC:

875

ESP6500AA

AF:

0.105

AC:

462

ESP6500EA

AF:

0.212

AC:

1822

ExAC

AF:

0.154

AC:

18753

Asia WGS

AF:

0.0930

AC:

323

AN:

3476

EpiCase

AF:

0.203

EpiControl

AF:

0.204

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.091

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

0.089

P;P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.072

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.20

B;B

Vest4

0.18

MPC

0.13

ClinPred

0.0022

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.48

gMVP

0.52

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over