rs2548538

chr5-96896438-T-Achr5-96896438-T-Cchr5-96896438-T-G

Variant summary

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

The NM_022350.5(ERAP2):c.1305T>A(p.Pro435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,612,288 control chromosomes in the GnomAD database, including 218,450 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 (22340 hom., cov: 31)
  • Exomes 𝑓: 0.52 (196110 hom.)
• Consequence: ERAP2 NM_022350.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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=-0.69).
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP2	NM_022350.5	c.1305T>A	p.Pro435=	synonymous_variant	8/19	ENST00000437043.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP2	ENST00000437043.8	c.1305T>A	p.Pro435=	synonymous_variant	8/19	1	NM_022350.5	P1
	ENST00000501338.5	n.1689-23060A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82245 AN: 151856 Hom.: 22338 Cov.: 31

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: 0.561

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.538

GnomAD3 exomes AF: 0.548 AC: 137286 AN: 250424 Hom.: 37975 AF XY: 0.547 AC XY: 74039 AN XY: 135410

Gnomad AFR exome AF: 0.576

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.575

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: 754400 AN: 1460314 Hom.: 196110 Cov.: 36 AF XY: 0.518 AC XY: 376450 AN XY: 726470

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: 0.525

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.541 AC: 82282 AN: 151974 Hom.: 22340 Cov.: 31 AF XY: 0.544 AC XY: 40378 AN XY: 74260

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.586

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: 0.525 Hom.: 6844

Bravo AF: 0.552

Asia WGS AF: 0.488 AC: 1698 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	-0.69
Cadd	Benign	7.1
Dann	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs2548538; hg19: chr5-96232142; COSMIC: COSV65939186; COSMIC: COSV65939186;