rs2910686

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022350.5(ERAP2):​c.2740-577T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,790 control chromosomes in the GnomAD database, including 13,267 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13267 hom., cov: 30)

Consequence

ERAP2
NM_022350.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.432
Variant links:
Genes affected
ERAP2 (HGNC:29499): (endoplasmic reticulum aminopeptidase 2) This gene encodes a zinc metalloaminopeptidase of the M1 protease family that resides in the endoplasmic reticulum and functions in N-terminal trimming antigenic epitopes for presentation by major histocompatibility complex (MHC) class I molecules. Certain mutations in this gene are associated with the inflammatory arthritis syndrome ankylosing spondylitis and pre-eclampsia. This gene is located adjacent to a closely related aminopeptidase gene on chromosome 5. [provided by RefSeq, Jul 2016]
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ERAP2NM_022350.5 linkuse as main transcriptc.2740-577T>C intron_variant ENST00000437043.8 NP_071745.1 Q6P179-1B2R769

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ERAP2ENST00000437043.8 linkuse as main transcriptc.2740-577T>C intron_variant 1 NM_022350.5 ENSP00000400376.3 Q6P179-1

Frequencies

GnomAD3 genomes
AF:
0.417
AC:
63215
AN:
151672
Hom.:
13243
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.417
Gnomad AMI
AF:
0.396
Gnomad AMR
AF:
0.345
Gnomad ASJ
AF:
0.324
Gnomad EAS
AF:
0.442
Gnomad SAS
AF:
0.393
Gnomad FIN
AF:
0.449
Gnomad MID
AF:
0.316
Gnomad NFE
AF:
0.434
Gnomad OTH
AF:
0.395
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.417
AC:
63298
AN:
151790
Hom.:
13267
Cov.:
30
AF XY:
0.416
AC XY:
30861
AN XY:
74148
show subpopulations
Gnomad4 AFR
AF:
0.417
Gnomad4 AMR
AF:
0.346
Gnomad4 ASJ
AF:
0.324
Gnomad4 EAS
AF:
0.441
Gnomad4 SAS
AF:
0.392
Gnomad4 FIN
AF:
0.449
Gnomad4 NFE
AF:
0.434
Gnomad4 OTH
AF:
0.399
Alfa
AF:
0.433
Hom.:
1781
Bravo
AF:
0.402
Asia WGS
AF:
0.499
AC:
1733
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
4.7
DANN
Benign
0.93

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: rs2910686; hg19: chr5-96252589; API