chr5-96790494-A-G

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

2

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]

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
ERAP1NM_001040458.3 linkuse as main transcriptc.1452+18T>C intron_variant ENST00000443439.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ERAP1ENST00000443439.7 linkuse as main transcriptc.1452+18T>C intron_variant 1 NM_001040458.3 P1Q9NZ08-1
ERAP1ENST00000296754.7 linkuse as main transcriptc.1452+18T>C intron_variant 1 Q9NZ08-2
ERAP1ENST00000507859.1 linkuse as main transcriptn.115+18T>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.624
AC:
94888
AN:
151968
Hom.:
29820
Cov.:
32
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.:
44
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.:
32
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 submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This 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.

Other links and lift over

dbSNP: rs27710; hg19: chr5-96126197; COSMIC: COSV57088465; COSMIC: COSV57088465; API