rs17486915

Variant names:

• chr5-96909015-T-C
• rs17486915
• NM_022350.5:c.2067T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022350.5(ERAP2):​c.2067T>C​(p.His689His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 1,614,024 control chromosomes in the GnomAD database, including 2,305 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 0.038 (189 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2116 hom.)
• Consequence: ERAP2 NM_022350.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-0.126 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP2	NM_022350.5	c.2067T>C	p.His689His	synonymous_variant	Exon 14 of 19	ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8	c.2067T>C	p.His689His	synonymous_variant	Exon 14 of 19	1	NM_022350.5	ENSP00000400376.3

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5772 AN: 152144 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.00992

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0285

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0589

GnomAD3 exomes AF: 0.0399 AC: 10042 AN: 251448 Hom.: 281 AF XY: 0.0415 AC XY: 5646 AN XY: 135904

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.0718

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0312

Gnomad FIN exome AF: 0.0194

Gnomad NFE exome AF: 0.0558

Gnomad OTH exome AF: 0.0508

GnomAD4 exome AF: 0.0506 AC: 74020 AN: 1461762 Hom.: 2116 Cov.: 32 AF XY: 0.0506 AC XY: 36783 AN XY: 727178

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.0352

Gnomad4 ASJ exome AF: 0.0687

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0314

Gnomad4 FIN exome AF: 0.0212

Gnomad4 NFE exome AF: 0.0564

Gnomad4 OTH exome AF: 0.0526

GnomAD4 genome AF: 0.0379 AC: 5768 AN: 152262 Hom.: 189 Cov.: 32 AF XY: 0.0361 AC XY: 2685 AN XY: 74464

Gnomad4 AFR AF: 0.00989

Gnomad4 AMR AF: 0.0460

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0559

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0557 Hom.: 318

Bravo AF: 0.0396

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0647

EpiControl AF: 0.0676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.8
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs17486915; hg19: chr5-96244719;