rs7714122

Positions:

• chr5-96919313-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP2	NM_022350.5	c.*1708T>C		3_prime_UTR_variant	19/19	ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8	c.*1708T>C		3_prime_UTR_variant	19/19	1	NM_022350.5	ENSP00000400376	P1
	ENST00000501338.5	n.1688+14809A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 EAS exome AF: 0.0735

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.0737

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0653

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0504

Gnomad4 NFE AF: 0.0675

Gnomad4 OTH AF: 0.0832

Alfa AF: 0.0721 Hom.: 547

Bravo AF: 0.0701

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs7714122; hg19: chr5-96255017;