rs1230358

chr5-96876037-T-G

Variant summary

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

The ENST00000501338.5(ENSG00000247121):n.1689-2659A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,154 control chromosomes in the GnomAD database, including 31,369 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 0.64 (31311 hom., cov: 30)
  • Exomes 𝑓: 0.62 (58 hom.)
• Consequence: ENST00000501338.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP2	NM_001130140.2	c.-176T>G		5_prime_UTR_variant	1/19
ERAP2	NM_001329229.1	c.-613T>G		5_prime_UTR_variant	1/18
ERAP2	NM_001329233.1	c.-613T>G		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000501338.5	n.1689-2659A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96907 AN: 151748 Hom.: 31287 Cov.: 30

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.622 AC: 179 AN: 288 Hom.: 58 Cov.: 0 AF XY: 0.641 AC XY: 91 AN XY: 142

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.691

Gnomad4 NFE exome AF: 0.656

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.639 AC: 96973 AN: 151866 Hom.: 31311 Cov.: 30 AF XY: 0.643 AC XY: 47696 AN XY: 74182

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.633

Alfa AF: 0.628 Hom.: 6446

Bravo AF: 0.650

Asia WGS AF: 0.650 AC: 2260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.2
Dann	Benign	0.36

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: rs1230358; hg19: chr5-96211741;