rs27042

chr5-96781236-G-Achr5-96781236-G-Cchr5-96781236-G-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.2448-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,592,212 control chromosomes in the GnomAD database, including 109,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11641 hom., cov: 29)
  • Exomes 𝑓: 0.36 (98355 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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=-0.81).
• BP6: Variant 5-96781236-G-A is Benign according to our data. Variant chr5-96781236-G-A is described in ClinVar as [Benign]. Clinvar id is 2688424.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3	c.2448-38C>T		intron_variant		ENST00000443439.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.2448-38C>T		intron_variant		1	NM_001040458.3	P1
ERAP1	ENST00000296754.7	c.2448-38C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58207 AN: 150544 Hom.: 11624 Cov.: 29

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.384

GnomAD3 exomes AF: 0.358 AC: 89127 AN: 249052 Hom.: 16865 AF XY: 0.369 AC XY: 49813 AN XY: 135112

Gnomad AFR exome AF: 0.484

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.365 AC: 525855 AN: 1441550 Hom.: 98355 Cov.: 27 AF XY: 0.370 AC XY: 265549 AN XY: 718326

Gnomad4 AFR exome AF: 0.476

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.387 AC: 58265 AN: 150662 Hom.: 11641 Cov.: 29 AF XY: 0.384 AC XY: 28240 AN XY: 73480

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.387

Alfa AF: 0.363 Hom.: 7420

Bravo AF: 0.384

Asia WGS AF: 0.395 AC: 1372 AN: 3476

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 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.3
Dann	Benign	0.62

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: rs27042; hg19: chr5-96116940; COSMIC: COSV57089350; COSMIC: COSV57089350;