Variant rs3213809 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001040458.3(ERAP1):c.1251C>T(p.His417His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,472 control chromosomes in the GnomAD database, including 14,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1232 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13156 hom. )

Consequence

ERAP1
NM_001040458.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.600

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 5-96792130-G-A is Benign according to our data. Variant chr5-96792130-G-A is described in ClinVar as [Benign]. Clinvar id is 2688437.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 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.1251C>T	p.His417His	synonymous_variant	8/19	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.1251C>T	p.His417His	synonymous_variant	8/19	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 linkuse as main transcript	c.1251C>T	p.His417His	synonymous_variant	8/20	1		ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000503311.1 linkuse as main transcript	n.335C>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16905

AN:

152048

Hom.:

1232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0314

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.0300

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.135

AC:

33966

AN:

251366

Hom.:

2671

AF XY:

0.134

AC XY:

18236

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.0284

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.131

AC:

190774

AN:

1461304

Hom.:

13156

Cov.:

AF XY:

0.131

AC XY:

95046

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.0287

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.0302

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.111

AC:

16906

AN:

152168

Hom.:

1232

Cov.:

AF XY:

0.114

AC XY:

8476

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0313

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.0301

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.119

Hom.:

943

Bravo

AF:

0.112

Asia WGS

AF:

0.0700

AC:

245

AN:

3478

EpiCase

AF:

0.138

EpiControl

AF:

0.140

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 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 36. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.6

DANN

Benign

0.69

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