dbSNP rs27042: ERAP1:c.2448-38C>T (chr5-96781236-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

Variant links:

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]

ERAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3 link	c.2448-38C>T		intron_variant	Intron 16 of 18	ENST00000443439.7	NP_001035548.1	Q9NZ08-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ERAP1	ENST00000443439.7 link	c.2448-38C>T	intron_variant	Intron 16 of 18	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 link	c.2448-38C>T	intron_variant	Intron 16 of 19	1		ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000512852.1 link	c.-57C>T	upstream_gene_variant		3		ENSP00000425381.1	H0Y9X5

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58207

AN:

150544

Hom.:

11624

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.370

AC XY:

265549

AN XY:

718326

show subpopulations

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.:

AF XY:

0.384

AC XY:

28240

AN XY:

73480

show subpopulations

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

LINK: link

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 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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over