Variant 5-96786556-T-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.1680-7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,581,154 control chromosomes in the GnomAD database, including 328,368 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 29766 hom., cov: 33)

Exomes 𝑓: 0.64 ( 298602 hom. )

Consequence

ERAP1
NM_001040458.3 splice_region, intron

Scores

Splicing: ADA: 0.00001424

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.300

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:

LOC124901031 (HGNC:):

LOC124901031 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=-0.84).

BP6

Variant 5-96786556-T-G is Benign according to our data. Variant chr5-96786556-T-G is described in ClinVar as [Benign]. Clinvar id is 2688357.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.1680-7A>C		splice_region_variant, 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.1680-7A>C	splice_region_variant, intron_variant	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.1680-7A>C	splice_region_variant, intron_variant	1		ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000507859.1 linkuse as main transcript	n.343-7A>C	splice_region_variant, intron_variant	2
ERAP1	ENST00000514604.5 linkuse as main transcript	n.104-7A>C	splice_region_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94748

AN:

151850

Hom.:

29736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.559

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:

154865

AN:

249884

Hom.:

48360

AF XY:

0.620

AC XY:

83759

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.607

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.553

Gnomad EAS exome

AF:

0.480

Gnomad SAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.644

AC:

920909

AN:

1429186

Hom.:

298602

Cov.:

AF XY:

0.643

AC XY:

458538

AN XY:

712986

show subpopulations

Gnomad4 AFR exome

AF:

0.596

Gnomad4 AMR exome

AF:

0.608

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.515

Gnomad4 SAS exome

AF:

0.586

Gnomad4 FIN exome

AF:

0.653

Gnomad4 NFE exome

AF:

0.660

Gnomad4 OTH exome

AF:

0.622

GnomAD4 genome

AF:

0.624

AC:

94824

AN:

151968

Hom.:

29766

Cov.:

AF XY:

0.621

AC XY:

46146

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.596

Gnomad4 ASJ

AF:

0.559

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.569

Alfa

AF:

0.640

Hom.:

13522

Bravo

AF:

0.616

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

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.5

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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