rs27710

Variant names:

• chr5-96790494-A-G
• rs27710
• NM_001040458.3:c.1452+18T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1452+18T>C		intron_variant	Intron 9 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1452+18T>C		intron_variant	Intron 9 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.1452+18T>C		intron_variant	Intron 9 of 19	1		ENSP00000296754.3
ERAP1	ENST00000507859.1	n.115+18T>C		intron_variant	Intron 1 of 4	2
ERAP1	ENST00000503311.1	n.*91T>C		downstream_gene_variant		4

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

GnomAD2 exomes AF: 0.620 AC: 155517 AN: 250896 AF XY: 0.620

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 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

African (AFR) AF: 0.598 AC: 20018 AN: 33462

American (AMR) AF: 0.608 AC: 27207 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 14591 AN: 26126

East Asian (EAS) AF: 0.515 AC: 20425 AN: 39652

South Asian (SAS) AF: 0.586 AC: 50553 AN: 86232

European-Finnish (FIN) AF: 0.653 AC: 34711 AN: 53166

Middle Eastern (MID) AF: 0.594 AC: 3425 AN: 5764

European-Non Finnish (NFE) AF: 0.661 AC: 734692 AN: 1111156

Other (OTH) AF: 0.623 AC: 37635 AN: 60380

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

African (AFR) AF: 0.605 AC: 25060 AN: 41452

American (AMR) AF: 0.596 AC: 9113 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1950 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2661 AN: 5172

South Asian (SAS) AF: 0.587 AC: 2830 AN: 4822

European-Finnish (FIN) AF: 0.646 AC: 6841 AN: 10584

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44750 AN: 67982

Other (OTH) AF: 0.569 AC: 1203 AN: 2116

Alfa AF: 0.632 Hom.: 7757

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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