rs2247650

Positions:

• chr5-96894046-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP2	NM_022350.5	c.1126-1200G>T		intron_variant		ENST00000437043.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP2	ENST00000437043.8	c.1126-1200G>T		intron_variant		1	NM_022350.5	P1
	ENST00000501338.5	n.1689-20668C>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.535

Alfa AF: 0.530 Hom.: 2664

Bravo AF: 0.553

Asia WGS AF: 0.493 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.73

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: rs2247650; hg19: chr5-96229750;