5-96792202-T-C

Variant names:

• chr5-96792202-T-C
• rs27640
• NM_001040458.3:c.1189-10A>G

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.1189-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,610,884 control chromosomes in the GnomAD database, including 465,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (39090 hom., cov: 32)
  • Exomes 𝑓: 0.76 (426837 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Scores: Splicing: ADA: 0.00007410
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68
• Publications: 16 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=-0.73).
• BP6: Variant 5-96792202-T-C is Benign according to our data. Variant chr5-96792202-T-C is described in ClinVar as [Benign]. Clinvar id is 2688537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1189-10A>G		intron_variant	Intron 7 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1189-10A>G		intron_variant	Intron 7 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.1189-10A>G		intron_variant	Intron 7 of 19	1		ENSP00000296754.3
ERAP1	ENST00000503311.1	n.273-10A>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108076 AN: 151932 Hom.: 39062 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.686

GnomAD2 exomes AF: 0.719 AC: 180404 AN: 251020 AF XY: 0.723

Gnomad AFR exome AF: 0.610

Gnomad AMR exome AF: 0.682

Gnomad ASJ exome AF: 0.684

Gnomad EAS exome AF: 0.482

Gnomad FIN exome AF: 0.772

Gnomad NFE exome AF: 0.788

Gnomad OTH exome AF: 0.731

GnomAD4 exome AF: 0.762 AC: 1111607 AN: 1458834 Hom.: 426837 Cov.: 34 AF XY: 0.761 AC XY: 552176 AN XY: 725842

African (AFR) AF: 0.602 AC: 20120 AN: 33416

American (AMR) AF: 0.685 AC: 30598 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17911 AN: 26100

East Asian (EAS) AF: 0.516 AC: 20467 AN: 39650

South Asian (SAS) AF: 0.669 AC: 57601 AN: 86162

European-Finnish (FIN) AF: 0.771 AC: 41156 AN: 53364

Middle Eastern (MID) AF: 0.707 AC: 4073 AN: 5764

European-Non Finnish (NFE) AF: 0.789 AC: 875371 AN: 1109378

Other (OTH) AF: 0.735 AC: 44310 AN: 60308

GnomAD4 genome AF: 0.711 AC: 108146 AN: 152050 Hom.: 39090 Cov.: 32 AF XY: 0.709 AC XY: 52686 AN XY: 74334

African (AFR) AF: 0.609 AC: 25248 AN: 41444

American (AMR) AF: 0.698 AC: 10665 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2387 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2667 AN: 5178

South Asian (SAS) AF: 0.672 AC: 3244 AN: 4826

European-Finnish (FIN) AF: 0.773 AC: 8165 AN: 10564

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53564 AN: 67972

Other (OTH) AF: 0.686 AC: 1442 AN: 2102

Alfa AF: 0.737 Hom.: 15243

Bravo AF: 0.699

Asia WGS AF: 0.626 AC: 2179 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 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.1
DANN	Benign	0.76
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000074
dbscSNV1_RF	Benign	0.090
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: rs27640; hg19: chr5-96127905; COSMIC: COSV57088486; COSMIC: COSV57088486;