rs27528

chr5-96800822-T-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.663+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,609,316 control chromosomes in the GnomAD database, including 51,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5058 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46856 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.290

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-96800822-T-C is Benign according to our data. Variant chr5-96800822-T-C is described in ClinVar as [Benign]. Clinvar id is 2688414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3	c.663+40A>G		intron_variant		ENST00000443439.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.663+40A>G		intron_variant		1	NM_001040458.3	P1
ERAP1	ENST00000296754.7	c.663+40A>G		intron_variant		1
ERAP1	ENST00000503921.5	c.-61+2581A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38642 AN: 152050 Hom.: 5051 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.272 AC: 68198 AN: 251024 Hom.: 9861 AF XY: 0.268 AC XY: 36366 AN XY: 135724

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.413

Gnomad ASJ exome AF: 0.257

Gnomad EAS exome AF: 0.173

Gnomad SAS exome AF: 0.280

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.251 AC: 365656 AN: 1457148 Hom.: 46856 Cov.: 30 AF XY: 0.252 AC XY: 182499 AN XY: 725208

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.254 AC: 38675 AN: 152168 Hom.: 5058 Cov.: 32 AF XY: 0.258 AC XY: 19181 AN XY: 74386

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.241

Alfa AF: 0.252 Hom.: 907

Bravo AF: 0.259

Asia WGS AF: 0.232 AC: 812 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 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.021
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: rs27528; hg19: chr5-96136525; COSMIC: COSV57086483; COSMIC: COSV57086483;