5-96908845-C-T

Variant names:

• chr5-96908845-C-T
• rs2549794
• NM_022350.5:c.2013-116C>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.2013-116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,070,790 control chromosomes in the GnomAD database, including 186,146 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 0.62 (29815 hom., cov: 32)
  • Exomes 𝑓: 0.58 (156331 hom.)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 90 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]

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP2	NM_022350.5	MANE Select	c.2013-116C>T		intron	N/A	NP_071745.1	Q6P179-1
	ERAP2	NM_001130140.3		c.2013-116C>T		intron	N/A	NP_001123612.1
	ERAP2	NM_001437802.1		c.1944-116C>T		intron	N/A	NP_001424731.1	A0AAQ5BHS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP2	ENST00000437043.8	TSL:1 MANE Select	c.2013-116C>T		intron	N/A	ENSP00000400376.3	Q6P179-1
	ERAP2	ENST00000379904.8	TSL:1	c.1878-116C>T		intron	N/A	ENSP00000369235.4	Q6P179-3
	ERAP2	ENST00000851668.1		c.2034-116C>T		intron	N/A	ENSP00000521727.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94911 AN: 151918 Hom.: 29799 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.579 AC: 531996 AN: 918754 Hom.: 156331 AF XY: 0.585 AC XY: 269726 AN XY: 461318

African (AFR) AF: 0.639 AC: 13025 AN: 20380

American (AMR) AF: 0.707 AC: 15730 AN: 22256

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 11763 AN: 16728

East Asian (EAS) AF: 0.709 AC: 23258 AN: 32782

South Asian (SAS) AF: 0.737 AC: 39858 AN: 54058

European-Finnish (FIN) AF: 0.624 AC: 25907 AN: 41522

Middle Eastern (MID) AF: 0.763 AC: 3042 AN: 3988

European-Non Finnish (NFE) AF: 0.546 AC: 374758 AN: 686038

Other (OTH) AF: 0.601 AC: 24655 AN: 41002

GnomAD4 genome AF: 0.625 AC: 94966 AN: 152036 Hom.: 29815 Cov.: 32 AF XY: 0.631 AC XY: 46894 AN XY: 74324

African (AFR) AF: 0.647 AC: 26839 AN: 41470

American (AMR) AF: 0.672 AC: 10265 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3472

East Asian (EAS) AF: 0.690 AC: 3579 AN: 5184

South Asian (SAS) AF: 0.734 AC: 3542 AN: 4826

European-Finnish (FIN) AF: 0.641 AC: 6763 AN: 10548

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39399 AN: 67948

Other (OTH) AF: 0.631 AC: 1332 AN: 2112

Alfa AF: 0.604 Hom.: 65707

Bravo AF: 0.633

Asia WGS AF: 0.638 AC: 2220 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	0.81
DANN	Benign	0.21
PhyloP100		-0.97
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: rs2549794; hg19: chr5-96244549;