rs27043

Variant names:

• chr5-96781596-G-A
• rs27043
• NM_001040458.3:c.2447+97C>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.2447+97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,491,934 control chromosomes in the GnomAD database, including 514,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (48588 hom., cov: 31)
  • Exomes 𝑓: 0.83 (466217 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.207

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=-0.66).
• BP6: Variant 5-96781596-G-A is Benign according to our data. Variant chr5-96781596-G-A is described in ClinVar as [Benign]. Clinvar id is 2688540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.2447+97C>T		intron_variant	Intron 16 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.2447+97C>T		intron_variant	Intron 16 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.2447+97C>T		intron_variant	Intron 16 of 19	1		ENSP00000296754.3
ERAP1	ENST00000514604.5	n.*98C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120844 AN: 151996 Hom.: 48544 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.832 AC: 1114529 AN: 1339820 Hom.: 466217 AF XY: 0.833 AC XY: 560637 AN XY: 673118

Gnomad4 AFR exome AF: 0.732

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.825

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.854

Gnomad4 OTH exome AF: 0.816

GnomAD4 genome AF: 0.795 AC: 120940 AN: 152114 Hom.: 48588 Cov.: 31 AF XY: 0.793 AC XY: 58939 AN XY: 74366

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.787

Alfa AF: 0.827 Hom.: 12289

Bravo AF: 0.785

Asia WGS AF: 0.711 AC: 2474 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 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.3
DANN	Benign	0.68

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: rs27043; hg19: chr5-96117300; COSMIC: COSV57088400; COSMIC: COSV57088400;