5-96890070-T-C

Variant names:

• chr5-96890070-T-C
• rs10434709
• NM_022350.5:c.970+765T>C

Variant summary

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

The NM_022350.5(ERAP2):​c.970+765T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,998 control chromosomes in the GnomAD database, including 22,940 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 0.55 (22940 hom., cov: 31)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 16 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 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.970+765T>C		intron	N/A	NP_071745.1
	ERAP2	NM_001130140.3		c.970+765T>C		intron	N/A	NP_001123612.1
	ERAP2	NM_001437802.1		c.970+765T>C		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.970+765T>C		intron	N/A	ENSP00000400376.3
	ERAP2	ENST00000379904.8	TSL:1	c.835+765T>C		intron	N/A	ENSP00000369235.4
	ERAP2	ENST00000510373.6	TSL:2	c.970+765T>C		intron	N/A	ENSP00000421175.2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83416 AN: 151880 Hom.: 22938 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.549 AC: 83452 AN: 151998 Hom.: 22940 Cov.: 31 AF XY: 0.550 AC XY: 40811 AN XY: 74260

African (AFR) AF: 0.559 AC: 23193 AN: 41470

American (AMR) AF: 0.599 AC: 9151 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2121 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2857 AN: 5160

South Asian (SAS) AF: 0.594 AC: 2857 AN: 4812

European-Finnish (FIN) AF: 0.510 AC: 5379 AN: 10540

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36041 AN: 67954

Other (OTH) AF: 0.560 AC: 1180 AN: 2108

Alfa AF: 0.525 Hom.: 8250

Bravo AF: 0.561

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.68
PhyloP100		0.15
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: rs10434709; hg19: chr5-96225774;