rs17486915

chr5-96909015-T-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.His689=) 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]

(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/exons	MANE	UniProt
ERAP2	NM_022350.5	c.2067T>C	p.His689=	synonymous_variant	14/19	ENST00000437043.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP2	ENST00000437043.8	c.2067T>C	p.His689=	synonymous_variant	14/19	1	NM_022350.5	P1
	ENST00000501338.5	n.1688+25107A>G		intron_variant, non_coding_transcript_variant		2

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;