rs2161657

Positions:

• chr5-96897102-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022350.5(ERAP2):​c.1503+239C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,940 control chromosomes in the GnomAD database, including 19,146 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 0.50 (19146 hom., cov: 31)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP2	NM_022350.5	c.1503+239C>T		intron_variant		ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8	c.1503+239C>T		intron_variant		1	NM_022350.5	ENSP00000400376.3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75915 AN: 151822 Hom.: 19153 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.500 AC: 75921 AN: 151940 Hom.: 19146 Cov.: 31 AF XY: 0.503 AC XY: 37333 AN XY: 74266

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.508

Alfa AF: 0.516 Hom.: 9354

Bravo AF: 0.503

Asia WGS AF: 0.470 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.81

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: rs2161657; hg19: chr5-96232806;