rs17481856

chr5-96781104-G-Achr5-96781104-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001040458.3(ERAP1):c.2542C>T(p.Leu848=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,464 control chromosomes in the GnomAD database, including 11,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (838 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10611 hom.)
• Consequence: ERAP1 NM_001040458.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.355

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-96781104-G-A is Benign according to our data. Variant chr5-96781104-G-A is described in ClinVar as [Benign]. Clinvar id is 2688519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.355 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3	c.2542C>T	p.Leu848=	synonymous_variant	17/19	ENST00000443439.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.2542C>T	p.Leu848=	synonymous_variant	17/19	1	NM_001040458.3	P1
ERAP1	ENST00000296754.7	c.2542C>T	p.Leu848=	synonymous_variant	17/20	1
ERAP1	ENST00000512852.1	c.79C>T	p.Leu27=	synonymous_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13879 AN: 151728 Hom.: 839 Cov.: 31

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.118

GnomAD3 exomes AF: 0.0998 AC: 25075 AN: 251366 Hom.: 1525 AF XY: 0.103 AC XY: 13999 AN XY: 135854

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.0725

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.00103

Gnomad SAS exome AF: 0.0767

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.116 AC: 169749 AN: 1461618 Hom.: 10611 Cov.: 33 AF XY: 0.116 AC XY: 84518 AN XY: 727114

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.0768

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.000555

Gnomad4 SAS exome AF: 0.0807

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.0914 AC: 13875 AN: 151846 Hom.: 838 Cov.: 31 AF XY: 0.0916 AC XY: 6794 AN XY: 74202

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0847

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.117

Alfa AF: 0.107 Hom.: 726

Bravo AF: 0.0872

Asia WGS AF: 0.0330 AC: 118 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.135

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 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.71
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17481856; hg19: chr5-96116808;