Variant 5-96803547-C-G 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.380G>C(p.Arg127Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,613,416 control chromosomes in the GnomAD database, including 381,926 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 0.63 ( 31291 hom., cov: 31)

Exomes 𝑓: 0.69 ( 350635 hom. )

Consequence

ERAP1
NM_001040458.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.537

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=2.399225E-6).

BP6

Variant 5-96803547-C-G is Benign according to our data. Variant chr5-96803547-C-G is described in ClinVar as [Benign]. Clinvar id is 2688544.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 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.380G>C	p.Arg127Pro	missense_variant	2/19	ENST00000443439.7	NP_001035548.1	Q9NZ08-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7 linkuse as main transcript	c.380G>C	p.Arg127Pro	missense_variant	2/19	1	NM_001040458.3	ENSP00000406304.2		Q9NZ08-1

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96341

AN:

151902

Hom.:

31278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.546

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.620

GnomAD3 exomes

AF:

0.637

AC:

160097

AN:

251238

Hom.:

52248

AF XY:

0.640

AC XY:

86937

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.526

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.580

Gnomad EAS exome

AF:

0.455

Gnomad SAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.716

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.689

AC:

1006403

AN:

1461396

Hom.:

350635

Cov.:

AF XY:

0.686

AC XY:

498432

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.514

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.585

Gnomad4 EAS exome

AF:

0.487

Gnomad4 SAS exome

AF:

0.541

Gnomad4 FIN exome

AF:

0.714

Gnomad4 NFE exome

AF:

0.721

Gnomad4 OTH exome

AF:

0.661

GnomAD4 genome

AF:

0.634

AC:

96391

AN:

152020

Hom.:

31291

Cov.:

AF XY:

0.631

AC XY:

46906

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.585

Gnomad4 ASJ

AF:

0.577

Gnomad4 EAS

AF:

0.485

Gnomad4 SAS

AF:

0.546

Gnomad4 FIN

AF:

0.719

Gnomad4 NFE

AF:

0.720

Gnomad4 OTH

AF:

0.621

Alfa

AF:

0.663

Hom.:

8915

Bravo

AF:

0.619

TwinsUK

AF:

0.711

AC:

2638

ALSPAC

AF:

0.713

AC:

2746

ESP6500AA

AF:

0.526

AC:

2319

ESP6500EA

AF:

0.709

AC:

6094

ExAC

AF:

0.638

AC:

77506

Asia WGS

AF:

0.568

AC:

1976

AN:

3478

EpiCase

AF:

0.712

EpiControl

AF:

0.704

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 84% of patients studied by a panel of primary immunodeficiencies. Number of patients: 74. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.8

DANN

Benign

0.65

DEOGEN2

Benign

0.0097

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.070

T;T;T

MetaRNN

Benign

0.0000024

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.6

N;N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

1.2

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.082

MPC

0.11

ClinPred

0.0071

GERP RS

3.7

Varity_R

0.61

gMVP

0.59

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