Variant rs2248374 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022350.5(ERAP2):c.1572+3A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,612,670 control chromosomes in the GnomAD database, including 218,571 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 0.54 ( 22361 hom., cov: 31)

Exomes 𝑓: 0.52 ( 196210 hom. )

Consequence

ERAP2
NM_022350.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.001093

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.823

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]

ERAP2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP2	NM_022350.5 linkuse as main transcript	c.1572+3A>G		splice_donor_region_variant, intron_variant		ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8 linkuse as main transcript	c.1572+3A>G		splice_donor_region_variant, intron_variant		1	NM_022350.5	ENSP00000400376	P1	Q6P179-1
	ENST00000501338.5 linkuse as main transcript	n.1689-26814T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82288

AN:

151886

Hom.:

22359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.584

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.579

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.548

AC:

137755

AN:

251208

Hom.:

38114

AF XY:

0.547

AC XY:

74279

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.575

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.588

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.527

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.517

AC:

754668

AN:

1460666

Hom.:

196210

Cov.:

AF XY:

0.518

AC XY:

376595

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.579

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.579

Gnomad4 EAS exome

AF:

0.540

Gnomad4 SAS exome

AF:

0.587

Gnomad4 FIN exome

AF:

0.526

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.542

AC:

82325

AN:

152004

Hom.:

22361

Cov.:

AF XY:

0.544

AC XY:

40407

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.572

Gnomad4 AMR

AF:

0.585

Gnomad4 ASJ

AF:

0.584

Gnomad4 EAS

AF:

0.556

Gnomad4 SAS

AF:

0.580

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.534

Alfa

AF:

0.530

Hom.:

10388

Bravo

AF:

0.552

Asia WGS

AF:

0.488

AC:

1700

AN:

3478

EpiCase

AF:

0.517

EpiControl

AF:

0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.064

SpliceAI score (max)

0.51

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.51

Position offset: -3

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over