rs1230361

Variant names:

• chr5-96877467-C-A
• rs1230361
• NM_022350.5:c.-123+940C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-96877467-C-A
• chr5-96877467-C-G
• chr5-96877467-C-T

Variant summary

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

The NM_022350.5(ERAP2):​c.-123+940C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,104 control chromosomes in the GnomAD database, including 21,000 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 0.52 (21000 hom., cov: 33)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP2	NM_022350.5	c.-123+940C>A		intron_variant	Intron 1 of 18	ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8	c.-123+940C>A		intron_variant	Intron 1 of 18	1	NM_022350.5	ENSP00000400376.3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79535 AN: 151986 Hom.: 20989 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.523 AC: 79574 AN: 152104 Hom.: 21000 Cov.: 33 AF XY: 0.526 AC XY: 39093 AN XY: 74350

African (AFR) AF: 0.566 AC: 23488 AN: 41482

American (AMR) AF: 0.530 AC: 8105 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1952 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2944 AN: 5178

South Asian (SAS) AF: 0.606 AC: 2930 AN: 4832

European-Finnish (FIN) AF: 0.512 AC: 5415 AN: 10566

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32986 AN: 67972

Other (OTH) AF: 0.523 AC: 1105 AN: 2112

Alfa AF: 0.496 Hom.: 17712

Bravo AF: 0.528

Asia WGS AF: 0.543 AC: 1887 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	3.0
DANN	Benign	0.39
PhyloP100		-0.22
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: rs1230361; hg19: chr5-96213171;