5-96913411-C-T

Variant names:

• chr5-96913411-C-T
• rs2255546
• NM_022350.5:c.2611C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022350.5(ERAP2):​c.2611C>T​(p.Leu871Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,613,122 control chromosomes in the GnomAD database, including 219,166 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 0.54 (22415 hom., cov: 32)
  • Exomes 𝑓: 0.52 (196751 hom.)
• Consequence: ERAP2 NM_022350.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 37 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.016).
• BP7: Synonymous conserved (PhyloP=-0.254 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.575 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.2611C>T	p.Leu871Leu	synonymous	Exon 17 of 19	NP_071745.1	Q6P179-1
	ERAP2	NM_001130140.3		c.2611C>T	p.Leu871Leu	synonymous	Exon 17 of 19	NP_001123612.1
	ERAP2	NM_001437802.1		c.2542C>T	p.Leu848Leu	synonymous	Exon 16 of 18	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.2611C>T	p.Leu871Leu	synonymous	Exon 17 of 19	ENSP00000400376.3	Q6P179-1
	ERAP2	ENST00000379904.8	TSL:1	c.2476C>T	p.Leu826Leu	synonymous	Exon 16 of 18	ENSP00000369235.4	Q6P179-3
	ERAP2	ENST00000851668.1		c.2632C>T	p.Leu878Leu	synonymous	Exon 17 of 19	ENSP00000521727.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82378 AN: 151916 Hom.: 22412 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.541

GnomAD2 exomes AF: 0.549 AC: 137798 AN: 250984 AF XY: 0.548

Gnomad AFR exome AF: 0.575

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.587

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.540

GnomAD4 exome AF: 0.517 AC: 755549 AN: 1461086 Hom.: 196751 Cov.: 43 AF XY: 0.519 AC XY: 377029 AN XY: 726832

African (AFR) AF: 0.579 AC: 19393 AN: 33474

American (AMR) AF: 0.618 AC: 27637 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 15706 AN: 26124

East Asian (EAS) AF: 0.535 AC: 21241 AN: 39690

South Asian (SAS) AF: 0.587 AC: 50584 AN: 86222

European-Finnish (FIN) AF: 0.525 AC: 28066 AN: 53410

Middle Eastern (MID) AF: 0.611 AC: 3522 AN: 5766

European-Non Finnish (NFE) AF: 0.502 AC: 557964 AN: 1111336

Other (OTH) AF: 0.521 AC: 31436 AN: 60356

GnomAD4 genome AF: 0.542 AC: 82417 AN: 152036 Hom.: 22415 Cov.: 32 AF XY: 0.545 AC XY: 40462 AN XY: 74308

African (AFR) AF: 0.572 AC: 23704 AN: 41474

American (AMR) AF: 0.586 AC: 8943 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2100 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2860 AN: 5164

South Asian (SAS) AF: 0.580 AC: 2795 AN: 4818

European-Finnish (FIN) AF: 0.532 AC: 5603 AN: 10534

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

European-Non Finnish (NFE) AF: 0.510 AC: 34668 AN: 67984

Other (OTH) AF: 0.536 AC: 1133 AN: 2114

Alfa AF: 0.531 Hom.: 33785

Bravo AF: 0.553

Asia WGS AF: 0.486 AC: 1691 AN: 3478

EpiCase AF: 0.517

EpiControl AF: 0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		-0.25
PromoterAI		-0.0056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2255546; hg19: chr5-96249115; COSMIC: COSV65940130; COSMIC: COSV65940130;