rs4869315

Variant names:

• chr5-96893568-G-A
• rs4869315
• NM_022350.5:c.1125+1115G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022350.5(ERAP2):​c.1125+1115G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,968 control chromosomes in the GnomAD database, including 16,123 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 0.46 (16123 hom., cov: 31)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 26 publications found

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]

ENSG00000247121 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP2	NM_022350.5	c.1125+1115G>A		intron_variant	Intron 6 of 18	ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8	c.1125+1115G>A		intron_variant	Intron 6 of 18	1	NM_022350.5	ENSP00000400376.3

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69324 AN: 151850 Hom.: 16121 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.475

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.456 AC: 69359 AN: 151968 Hom.: 16123 Cov.: 31 AF XY: 0.454 AC XY: 33710 AN XY: 74272

African (AFR) AF: 0.524 AC: 21735 AN: 41448

American (AMR) AF: 0.488 AC: 7443 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1785 AN: 3466

East Asian (EAS) AF: 0.454 AC: 2344 AN: 5162

South Asian (SAS) AF: 0.497 AC: 2396 AN: 4822

European-Finnish (FIN) AF: 0.353 AC: 3725 AN: 10552

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28385 AN: 67946

Other (OTH) AF: 0.471 AC: 992 AN: 2108

Alfa AF: 0.443 Hom.: 29969

Bravo AF: 0.474

Asia WGS AF: 0.408 AC: 1421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.92
DANN	Benign	0.37
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4869315; hg19: chr5-96229272;