rs2910686

chr5-96916885-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.2740-577T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,790 control chromosomes in the GnomAD database, including 13,267 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 0.42 (13267 hom., cov: 30)
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP2	NM_022350.5	c.2740-577T>C		intron_variant		ENST00000437043.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP2	ENST00000437043.8	c.2740-577T>C		intron_variant		1	NM_022350.5	P1
	ENST00000501338.5	n.1688+17237A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63215 AN: 151672 Hom.: 13243 Cov.: 30

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.417 AC: 63298 AN: 151790 Hom.: 13267 Cov.: 30 AF XY: 0.416 AC XY: 30861 AN XY: 74148

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.399

Alfa AF: 0.433 Hom.: 1781

Bravo AF: 0.402

Asia WGS AF: 0.499 AC: 1733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	4.7
Dann	Benign	0.93

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: rs2910686; hg19: chr5-96252589;