rs30186

Positions:

• chr5-96788744-G-C

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.1525-59C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 1,590,662 control chromosomes in the GnomAD database, including 460,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (39568 hom., cov: 31)
  • Exomes 𝑓: 0.76 (421423 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.864

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]

ERAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-96788744-G-C is Benign according to our data. Variant chr5-96788744-G-C is described in ClinVar as [Benign]. Clinvar id is 2688536.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1525-59C>G		intron_variant		ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1525-59C>G		intron_variant		1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.1525-59C>G		intron_variant		1		ENSP00000296754.3
ERAP1	ENST00000507859.1	n.188-59C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108840 AN: 151930 Hom.: 39539 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.763 AC: 1097365 AN: 1438616 Hom.: 421423 AF XY: 0.761 AC XY: 544111 AN XY: 714556

Gnomad4 AFR exome AF: 0.618

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.770

Gnomad4 NFE exome AF: 0.789

Gnomad4 OTH exome AF: 0.736

GnomAD4 genome AF: 0.716 AC: 108913 AN: 152046 Hom.: 39568 Cov.: 31 AF XY: 0.713 AC XY: 53026 AN XY: 74320

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.688

Alfa AF: 0.757 Hom.: 5476

Bravo AF: 0.705

Asia WGS AF: 0.627 AC: 2184 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 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.33

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: rs30186; hg19: chr5-96124447; COSMIC: COSV57087182; COSMIC: COSV57087182;