rs3849749

Positions:

• chr5-96898829-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022350.5(ERAP2):​c.1504-1292A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,000 control chromosomes in the GnomAD database, including 29,722 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 (29722 hom., cov: 32)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP2	NM_022350.5	c.1504-1292A>T		intron_variant		ENST00000437043.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP2	ENST00000437043.8	c.1504-1292A>T		intron_variant		1	NM_022350.5	P1
	ENST00000501338.5	n.1689-25451T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94759 AN: 151882 Hom.: 29708 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.624 AC: 94812 AN: 152000 Hom.: 29722 Cov.: 32 AF XY: 0.630 AC XY: 46811 AN XY: 74296

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.628

Alfa AF: 0.599 Hom.: 3409

Bravo AF: 0.632

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs3849749; hg19: chr5-96234533;