Variant rs27528 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.663+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,609,316 control chromosomes in the GnomAD database, including 51,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5058 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46856 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.290

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=-0.88).

BP6

Variant 5-96800822-T-C is Benign according to our data. Variant chr5-96800822-T-C is described in ClinVar as [Benign]. Clinvar id is 2688414.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3 link	c.663+40A>G		intron_variant	Intron 3 of 18	ENST00000443439.7	NP_001035548.1	Q9NZ08-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ERAP1	ENST00000443439.7 link	c.663+40A>G	intron_variant	Intron 3 of 18	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 link	c.663+40A>G	intron_variant	Intron 3 of 19	1		ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000503921.5 link	c.-61+2581A>G	intron_variant	Intron 2 of 2	4		ENSP00000427025.1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38642

AN:

152050

Hom.:

5051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.272

AC:

68198

AN:

251024

Hom.:

9861

AF XY:

0.268

AC XY:

36366

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.413

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.173

Gnomad SAS exome

AF:

0.280

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.247

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.251

AC:

365656

AN:

1457148

Hom.:

46856

Cov.:

AF XY:

0.252

AC XY:

182499

AN XY:

725208

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.254

Gnomad4 EAS exome

AF:

0.210

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

AF:

0.254

AC:

38675

AN:

152168

Hom.:

5058

Cov.:

AF XY:

0.258

AC XY:

19181

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.325

Gnomad4 ASJ

AF:

0.261

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.252

Hom.:

907

Bravo

AF:

0.259

Asia WGS

AF:

0.232

AC:

812

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.021

DANN

Benign

0.43

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