Variant 5-96788627-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 ENST00000443439.7(ERAP1):c.1583A>G(p.Lys528Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,613,788 control chromosomes in the GnomAD database, including 336,155 homozygotes. In-silico tool predicts 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 0.62 ( 29841 hom., cov: 32)

Exomes 𝑓: 0.65 ( 306314 hom. )

Consequence

ERAP1
ENST00000443439.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.43

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2251857E-4).

BP6

Variant 5-96788627-T-C is Benign according to our data. Variant chr5-96788627-T-C is described in ClinVar as [Benign]. Clinvar id is 2688359.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 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.1583A>G	p.Lys528Arg	missense_variant	11/19	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.1583A>G	p.Lys528Arg	missense_variant	11/19	1	NM_001040458.3	ENSP00000406304	P1	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.1583A>G	p.Lys528Arg	missense_variant	11/20	1		ENSP00000296754		Q9NZ08-2
ERAP1	ENST00000507859.1 linkuse as main transcript	n.246A>G		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94853

AN:

151930

Hom.:

29810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.567

GnomAD3 exomes

AF:

0.620

AC:

155788

AN:

251240

Hom.:

48690

AF XY:

0.621

AC XY:

84267

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.611

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.480

Gnomad SAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.646

AC:

943908

AN:

1461740

Hom.:

306314

Cov.:

AF XY:

0.644

AC XY:

468530

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.598

Gnomad4 AMR exome

AF:

0.609

Gnomad4 ASJ exome

AF:

0.559

Gnomad4 EAS exome

AF:

0.515

Gnomad4 SAS exome

AF:

0.586

Gnomad4 FIN exome

AF:

0.653

Gnomad4 NFE exome

AF:

0.661

Gnomad4 OTH exome

AF:

0.623

GnomAD4 genome

AF:

0.624

AC:

94930

AN:

152048

Hom.:

29841

Cov.:

AF XY:

0.621

AC XY:

46193

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.604

Gnomad4 AMR

AF:

0.596

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.513

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.569

Alfa

AF:

0.638

Hom.:

76596

Bravo

AF:

0.617

TwinsUK

AF:

0.660

AC:

2447

ALSPAC

AF:

0.660

AC:

2544

ESP6500AA

AF:

0.597

AC:

2629

ESP6500EA

AF:

0.643

AC:

5533

ExAC

AF:

0.620

AC:

75310

Asia WGS

AF:

0.593

AC:

2063

AN:

3478

EpiCase

AF:

0.652

EpiControl

AF:

0.641

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 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.00012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.7

H;H

MutationTaster

Benign

0.0013

P;P;P

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.18

Sift

Benign

0.073

T;T

Sift4G

Benign

0.10

T;T

Polyphen

1.0

D;D

Vest4

0.14

MPC

0.19

ClinPred

0.10

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.61

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

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