rs27710

chr5-96790494-A-G

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.1452+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,612,748 control chromosomes in the GnomAD database, including 336,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29851 hom., cov: 32)
  • Exomes 𝑓: 0.65 (306196 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.281

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=-0.79).
• BP6: Variant 5-96790494-A-G is Benign according to our data. Variant chr5-96790494-A-G is described in ClinVar as [Benign]. Clinvar id is 2688361.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.1452+18T>C		intron_variant		ENST00000443439.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.1452+18T>C		intron_variant		1	NM_001040458.3	P1
ERAP1	ENST00000296754.7	c.1452+18T>C		intron_variant		1
ERAP1	ENST00000507859.1	n.115+18T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94888 AN: 151968 Hom.: 29820 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.567

GnomAD3 exomes AF: 0.620 AC: 155517 AN: 250896 Hom.: 48606 AF XY: 0.620 AC XY: 84140 AN XY: 135648

Gnomad AFR exome AF: 0.607

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.480

Gnomad SAS exome AF: 0.594

Gnomad FIN exome AF: 0.653

Gnomad NFE exome AF: 0.654

Gnomad OTH exome AF: 0.616

GnomAD4 exome AF: 0.646 AC: 943257 AN: 1460662 Hom.: 306196 Cov.: 44 AF XY: 0.644 AC XY: 468243 AN XY: 726698

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.608

Gnomad4 ASJ exome AF: 0.558

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.661

Gnomad4 OTH exome AF: 0.623

GnomAD4 genome AF: 0.624 AC: 94965 AN: 152086 Hom.: 29851 Cov.: 32 AF XY: 0.622 AC XY: 46205 AN XY: 74338

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.569

Alfa AF: 0.632 Hom.: 7612

Bravo AF: 0.617

Asia WGS AF: 0.592 AC: 2060 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	-0.79
Cadd	Benign	7.3
Dann	Benign	0.76

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: rs27710; hg19: chr5-96126197; COSMIC: COSV57088465; COSMIC: COSV57088465;