chr5-96917099-G-A

Variant names:

• chr5-96917099-G-A
• rs1363907
• NM_022350.5:c.2740-363G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022350.5(ERAP2):​c.2740-363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,992 control chromosomes in the GnomAD database, including 10,902 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 0.38 (10902 hom., cov: 31)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516
• Publications: 73 publications found

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]

ENSG00000247121 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022350.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP2	NM_022350.5	MANE Select	c.2740-363G>A		intron	N/A	NP_071745.1
	ERAP2	NM_001130140.3		c.2740-363G>A		intron	N/A	NP_001123612.1
	ERAP2	NM_001437802.1		c.2671-363G>A		intron	N/A	NP_001424731.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP2	ENST00000437043.8	TSL:1 MANE Select	c.2740-363G>A		intron	N/A	ENSP00000400376.3
	ERAP2	ENST00000379904.8	TSL:1	c.2605-363G>A		intron	N/A	ENSP00000369235.4
	ERAP2	ENST00000510373.6	TSL:2	c.2740-363G>A		intron	N/A	ENSP00000421175.2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57081 AN: 151874 Hom.: 10882 Cov.: 31

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.376 AC: 57143 AN: 151992 Hom.: 10902 Cov.: 31 AF XY: 0.370 AC XY: 27454 AN XY: 74284

African (AFR) AF: 0.354 AC: 14654 AN: 41440

American (AMR) AF: 0.328 AC: 5008 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3468

East Asian (EAS) AF: 0.312 AC: 1609 AN: 5160

South Asian (SAS) AF: 0.266 AC: 1284 AN: 4820

European-Finnish (FIN) AF: 0.361 AC: 3802 AN: 10546

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.420 AC: 28576 AN: 67964

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.401 Hom.: 19791

Bravo AF: 0.367

Asia WGS AF: 0.361 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.66
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1363907; hg19: chr5-96252803;