rs42398

chr5-96784751-C-T

Variant summary

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

The NM_001040458.3(ERAP1):c.1944-671G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,668 control chromosomes in the GnomAD database, including 48,727 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 0.79 (48537 hom., cov: 31)
  • Exomes 𝑓: 0.79 (190 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

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]

LOC124901031 (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 (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3	c.1944-671G>A		intron_variant		ENST00000443439.7
LOC124901031	XR_007058877.1	n.672C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.1944-671G>A		intron_variant		1	NM_001040458.3	P1
ERAP1	ENST00000296754.7	c.1944-671G>A		intron_variant		1
ERAP1	ENST00000514604.5	n.368-671G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000512856.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120760 AN: 151948 Hom.: 48492 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.786

GnomAD4 exome AF: 0.792 AC: 475 AN: 600 Hom.: 190 Cov.: 0 AF XY: 0.803 AC XY: 252 AN XY: 314

Gnomad4 AMR exome AF: 0.622

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.708

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.825

Gnomad4 OTH exome AF: 0.808

GnomAD4 genome AF: 0.795 AC: 120856 AN: 152068 Hom.: 48537 Cov.: 31 AF XY: 0.792 AC XY: 58896 AN XY: 74350

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.787

Alfa AF: 0.837 Hom.: 108970

Bravo AF: 0.785

Asia WGS AF: 0.712 AC: 2478 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	0.11
Dann	Benign	0.18

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: rs42398; hg19: chr5-96120455;