rs1230358

Variant names:

• chr5-96876037-T-G
• rs1230358
• NM_001130140.2:c.-176T>G

Variant summary

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

The NM_001130140.2(ERAP2):​c.-176T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,154 control chromosomes in the GnomAD database, including 31,369 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 0.64 (31311 hom., cov: 30)
  • Exomes 𝑓: 0.62 (58 hom.)
• Consequence: ERAP2 NM_001130140.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP2	NM_001130140.2	c.-176T>G		5_prime_UTR_variant	Exon 1 of 19		NP_001123612.1
ERAP2	NM_001329229.1	c.-613T>G		5_prime_UTR_variant	Exon 1 of 18		NP_001316158.1
ERAP2	NM_001329233.1	c.-613T>G		5_prime_UTR_variant	Exon 1 of 5		NP_001316162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000510373	c.-176T>G		5_prime_UTR_variant	Exon 1 of 19	2		ENSP00000421175.2
ENSG00000247121	ENST00000501338.5	n.1689-2659A>C		intron_variant	Intron 1 of 3	2
ENSG00000247121	ENST00000655392.1	n.819-2365A>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96907 AN: 151748 Hom.: 31287 Cov.: 30

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.622 AC: 179 AN: 288 Hom.: 58 Cov.: 0 AF XY: 0.641 AC XY: 91 AN XY: 142

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.691

Gnomad4 NFE exome AF: 0.656

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.639 AC: 96973 AN: 151866 Hom.: 31311 Cov.: 30 AF XY: 0.643 AC XY: 47696 AN XY: 74182

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.633

Alfa AF: 0.628 Hom.: 6446

Bravo AF: 0.650

Asia WGS AF: 0.650 AC: 2260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.36

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: rs1230358; hg19: chr5-96211741;