rs469758

chr5-96786011-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001040458.3(ERAP1):c.1760-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,593,676 control chromosomes in the GnomAD database, including 331,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29780 hom., cov: 32)
  • Exomes 𝑓: 0.65 (301809 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.131

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-96786011-C-T is Benign according to our data. Variant chr5-96786011-C-T is described in ClinVar as [Benign]. Clinvar id is 2688356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3	c.1760-40G>A		intron_variant		ENST00000443439.7
LOC124901031	XR_007058877.1	n.1616C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.1760-40G>A		intron_variant		1	NM_001040458.3	P1
	ENST00000512856.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94786 AN: 151970 Hom.: 29750 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.565

GnomAD3 exomes AF: 0.620 AC: 151933 AN: 244978 Hom.: 47266 AF XY: 0.621 AC XY: 82411 AN XY: 132750

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.553

Gnomad EAS exome AF: 0.482

Gnomad SAS exome AF: 0.596

Gnomad FIN exome AF: 0.655

Gnomad NFE exome AF: 0.654

Gnomad OTH exome AF: 0.615

GnomAD4 exome AF: 0.645 AC: 930518 AN: 1441588 Hom.: 301809 Cov.: 26 AF XY: 0.644 AC XY: 462599 AN XY: 718260

Gnomad4 AFR exome AF: 0.596

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.661

Gnomad4 OTH exome AF: 0.623

GnomAD4 genome AF: 0.624 AC: 94862 AN: 152088 Hom.: 29780 Cov.: 32 AF XY: 0.621 AC XY: 46163 AN XY: 74340

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.566

Alfa AF: 0.632 Hom.: 6218

Bravo AF: 0.616

Asia WGS AF: 0.592 AC: 2061 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	9.7
Dann	Benign	0.43

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: rs469758; hg19: chr5-96121715; COSMIC: COSV57085106; COSMIC: COSV57085106;