5-96890070-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP2	NM_022350.5	c.970+765T>C		intron_variant	Intron 5 of 18	ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8	c.970+765T>C		intron_variant	Intron 5 of 18	1	NM_022350.5	ENSP00000400376.3

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

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.560

Alfa AF: 0.519 Hom.: 6412

Bravo AF: 0.561

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.68

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: rs10434709; hg19: chr5-96225774;