rs7714122

Variant names:

• chr5-96919313-T-C
• rs7714122
• NM_022350.5:c.*1708T>C

Variant summary

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

The NM_022350.5(ERAP2):​c.*1708T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 152,440 control chromosomes in the GnomAD database, including 458 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 0.070 (458 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: ERAP2 NM_022350.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• 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]

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 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.*1708T>C		3_prime_UTR	Exon 19 of 19	NP_071745.1	Q6P179-1
	ERAP2	NM_001130140.3		c.*1708T>C		3_prime_UTR	Exon 19 of 19	NP_001123612.1
	ERAP2	NM_001437802.1		c.*1708T>C		3_prime_UTR	Exon 18 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.*1708T>C		3_prime_UTR	Exon 19 of 19	ENSP00000400376.3	Q6P179-1
	ERAP2	ENST00000851668.1		c.*1708T>C		3_prime_UTR	Exon 19 of 19	ENSP00000521727.1
	ERAP2	ENST00000510373.6	TSL:2	c.*1708T>C		3_prime_UTR	Exon 19 of 19	ENSP00000421175.2	Q6P179-1

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10711 AN: 152182 Hom.: 458 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0654

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.0831

GnomAD4 exome AF: 0.0714 AC: 10 AN: 140 Hom.: 0 Cov.: 0 AF XY: 0.0789 AC XY: 6 AN XY: 76

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0735 AC: 10 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0704 AC: 10726 AN: 152300 Hom.: 458 Cov.: 32 AF XY: 0.0708 AC XY: 5274 AN XY: 74478

African (AFR) AF: 0.0737 AC: 3063 AN: 41556

American (AMR) AF: 0.0602 AC: 921 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3470

East Asian (EAS) AF: 0.0653 AC: 339 AN: 5188

South Asian (SAS) AF: 0.117 AC: 566 AN: 4832

European-Finnish (FIN) AF: 0.0504 AC: 535 AN: 10614

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4594 AN: 68020

Other (OTH) AF: 0.0832 AC: 176 AN: 2116

Alfa AF: 0.0714 Hom.: 720

Bravo AF: 0.0701

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7714122; hg19: chr5-96255017;