Variant 5-96792202-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.1189-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,610,884 control chromosomes in the GnomAD database, including 465,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.71 ( 39090 hom., cov: 32)

Exomes 𝑓: 0.76 ( 426837 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Splicing: ADA: 0.00007410

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68

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:

ERAP1 (HGNC:):

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 (BayesDel_noAF=-0.73).

BP6

Variant 5-96792202-T-C is Benign according to our data. Variant chr5-96792202-T-C is described in ClinVar as [Benign]. Clinvar id is 2688537.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 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.1189-10A>G		intron_variant		ENST00000443439.7	NP_001035548.1	Q9NZ08-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ERAP1	ENST00000443439.7 linkuse as main transcript	c.1189-10A>G	intron_variant	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.1189-10A>G	intron_variant	1		ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000503311.1 linkuse as main transcript	n.273-10A>G	intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.711

AC:

108076

AN:

151932

Hom.:

39062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.609

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.697

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.773

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.788

Gnomad OTH

AF:

0.686

GnomAD3 exomes

AF:

0.719

AC:

180404

AN:

251020

Hom.:

65865

AF XY:

0.723

AC XY:

98068

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.610

Gnomad AMR exome

AF:

0.682

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.482

Gnomad SAS exome

AF:

0.673

Gnomad FIN exome

AF:

0.772

Gnomad NFE exome

AF:

0.788

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.762

AC:

1111607

AN:

1458834

Hom.:

426837

Cov.:

AF XY:

0.761

AC XY:

552176

AN XY:

725842

show subpopulations

Gnomad4 AFR exome

AF:

0.602

Gnomad4 AMR exome

AF:

0.685

Gnomad4 ASJ exome

AF:

0.686

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.669

Gnomad4 FIN exome

AF:

0.771

Gnomad4 NFE exome

AF:

0.789

Gnomad4 OTH exome

AF:

0.735

GnomAD4 genome

AF:

0.711

AC:

108146

AN:

152050

Hom.:

39090

Cov.:

AF XY:

0.709

AC XY:

52686

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.609

Gnomad4 AMR

AF:

0.698

Gnomad4 ASJ

AF:

0.688

Gnomad4 EAS

AF:

0.515

Gnomad4 SAS

AF:

0.672

Gnomad4 FIN

AF:

0.773

Gnomad4 NFE

AF:

0.788

Gnomad4 OTH

AF:

0.686

Alfa

AF:

0.724

Hom.:

8975

Bravo

AF:

0.699

Asia WGS

AF:

0.626

AC:

2179

AN:

3478

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 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.1

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000074

dbscSNV1_RF

Benign

0.090

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