Variant 5-96790494-A-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.1452+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,612,748 control chromosomes in the GnomAD database, including 336,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 29851 hom., cov: 32)

Exomes 𝑓: 0.65 ( 306196 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.281

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 (BayesDel_noAF=-0.79).

BP6

Variant 5-96790494-A-G is Benign according to our data. Variant chr5-96790494-A-G is described in ClinVar as [Benign]. Clinvar id is 2688361.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	UniProt
ERAP1	NM_001040458.3 linkuse as main transcript	c.1452+18T>C		intron_variant		ENST00000443439.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7 linkuse as main transcript	c.1452+18T>C	intron_variant	1	NM_001040458.3	P1	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.1452+18T>C	intron_variant	1			Q9NZ08-2
ERAP1	ENST00000507859.1 linkuse as main transcript	n.115+18T>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94888

AN:

151968

Hom.:

29820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.596

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.515

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:

155517

AN:

250896

Hom.:

48606

AF XY:

0.620

AC XY:

84140

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.607

Gnomad AMR exome

AF:

0.610

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:

0.616

GnomAD4 exome

AF:

0.646

AC:

943257

AN:

1460662

Hom.:

306196

Cov.:

AF XY:

0.644

AC XY:

468243

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.598

Gnomad4 AMR exome

AF:

0.608

Gnomad4 ASJ exome

AF:

0.558

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:

94965

AN:

152086

Hom.:

29851

Cov.:

AF XY:

0.622

AC XY:

46205

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.605

Gnomad4 AMR

AF:

0.596

Gnomad4 ASJ

AF:

0.562

Gnomad4 EAS

AF:

0.515

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.569

Alfa

AF:

0.632

Hom.:

7612

Bravo

AF:

0.617

Asia WGS

AF:

0.592

AC:

2060

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 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

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.3

DANN

Benign

0.76

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