Variant 5-96781104-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001040458.3(ERAP1):c.2542C>T(p.Leu848Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,464 control chromosomes in the GnomAD database, including 11,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.091 ( 838 hom., cov: 31)

Exomes 𝑓: 0.12 ( 10611 hom. )

Consequence

ERAP1
NM_001040458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.355

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-96781104-G-A is Benign according to our data. Variant chr5-96781104-G-A is described in ClinVar as [Benign]. Clinvar id is 2688519.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.355 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 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.2542C>T	p.Leu848Leu	synonymous_variant	17/19	ENST00000443439.7	NP_001035548.1	Q9NZ08-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ERAP1	ENST00000443439.7 linkuse as main transcript	c.2542C>T	p.Leu848Leu	synonymous_variant	17/19	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.2542C>T	p.Leu848Leu	synonymous_variant	17/20	1		ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000512852.1 linkuse as main transcript	c.76C>T	p.Leu26Leu	synonymous_variant	1/4	3		ENSP00000425381.1	H0Y9X5

Frequencies

GnomAD3 genomes

AF:

0.0915

AC:

13879

AN:

151728

Hom.:

839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0844

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.0998

AC:

25075

AN:

251366

Hom.:

1525

AF XY:

0.103

AC XY:

13999

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.0725

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.00103

Gnomad SAS exome

AF:

0.0767

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.116

AC:

169749

AN:

1461618

Hom.:

10611

Cov.:

AF XY:

0.116

AC XY:

84518

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0198

Gnomad4 AMR exome

AF:

0.0768

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.000555

Gnomad4 SAS exome

AF:

0.0807

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.0914

AC:

13875

AN:

151846

Hom.:

838

Cov.:

AF XY:

0.0916

AC XY:

6794

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0847

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.107

Hom.:

726

Bravo

AF:

0.0872

Asia WGS

AF:

0.0330

AC:

118

AN:

3478

EpiCase

AF:

0.132

EpiControl

AF:

0.135

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 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.71

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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