rs3733904

Positions:

• chr5-96880469-A-G

Variant summary

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

The ENST00000437043.8(ERAP2):​c.575+209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,260 control chromosomes in the GnomAD database, including 2,284 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 0.15 (2284 hom., cov: 33)
• Consequence: ERAP2 ENST00000437043.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP2	NM_022350.5	c.575+209A>G		intron_variant		ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8	c.575+209A>G		intron_variant		1	NM_022350.5	ENSP00000400376	P1
	ENST00000501338.5	n.1689-7091T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23422 AN: 152142 Hom.: 2288 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.154 AC: 23412 AN: 152260 Hom.: 2284 Cov.: 33 AF XY: 0.153 AC XY: 11368 AN XY: 74434

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0683

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.197

Alfa AF: 0.211 Hom.: 4738

Bravo AF: 0.146

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.69

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: rs3733904; hg19: chr5-96216173;