rs2247650

Variant names:

• chr5-96894046-G-T
• rs2247650
• NM_022350.5:c.1126-1200G>T

Variant summary

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

The NM_022350.5(ERAP2):​c.1126-1200G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,034 control chromosomes in the GnomAD database, including 22,541 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 (22541 hom., cov: 32)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 10 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]

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]

ENSG00000247121 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022350.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP2	NM_022350.5	MANE Select	c.1126-1200G>T		intron	N/A	NP_071745.1	Q6P179-1
	ERAP2	NM_001130140.3		c.1126-1200G>T		intron	N/A	NP_001123612.1
	ERAP2	NM_001437802.1		c.1126-1200G>T		intron	N/A	NP_001424731.1	A0AAQ5BHS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP2	ENST00000437043.8	TSL:1 MANE Select	c.1126-1200G>T		intron	N/A	ENSP00000400376.3	Q6P179-1
	ERAP2	ENST00000379904.8	TSL:1	c.991-1200G>T		intron	N/A	ENSP00000369235.4	Q6P179-3
	ERAP2	ENST00000851668.1		c.1126-1200G>T		intron	N/A	ENSP00000521727.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82623 AN: 151916 Hom.: 22538 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.544 AC: 82660 AN: 152034 Hom.: 22541 Cov.: 32 AF XY: 0.546 AC XY: 40583 AN XY: 74308

African (AFR) AF: 0.569 AC: 23598 AN: 41472

American (AMR) AF: 0.584 AC: 8924 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2014 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2869 AN: 5162

South Asian (SAS) AF: 0.585 AC: 2824 AN: 4826

European-Finnish (FIN) AF: 0.542 AC: 5718 AN: 10552

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34973 AN: 67964

Other (OTH) AF: 0.535 AC: 1127 AN: 2108

Alfa AF: 0.531 Hom.: 2782

Bravo AF: 0.553

Asia WGS AF: 0.493 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.73
PhyloP100		0.090
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: rs2247650; hg19: chr5-96229750;