rs17481856

Variant names:

• chr5-96781104-G-A
• rs17481856
• NM_001040458.3:c.2542C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-96781104-G-A
• chr5-96781104-G-C
• chr5-96781104-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001040458.3(ERAP1):​c.2542C>T​(p.Leu848Leu) 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
• Publications: 25 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 -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 VariationId 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 rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.2542C>T	p.Leu848Leu	synonymous_variant	Exon 17 of 19	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.2542C>T	p.Leu848Leu	synonymous_variant	Exon 17 of 19	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.2542C>T	p.Leu848Leu	synonymous_variant	Exon 17 of 20	1		ENSP00000296754.3
ERAP1	ENST00000512852.1	c.76C>T	p.Leu26Leu	synonymous_variant	Exon 1 of 4	3		ENSP00000425381.1

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

GnomAD2 exomes AF: 0.0998 AC: 25075 AN: 251366 AF XY: 0.103

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 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

African (AFR) AF: 0.0198 AC: 663 AN: 33480

American (AMR) AF: 0.0768 AC: 3433 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3311 AN: 26128

East Asian (EAS) AF: 0.000555 AC: 22 AN: 39666

South Asian (SAS) AF: 0.0807 AC: 6957 AN: 86250

European-Finnish (FIN) AF: 0.119 AC: 6333 AN: 53418

Middle Eastern (MID) AF: 0.113 AC: 653 AN: 5768

European-Non Finnish (NFE) AF: 0.127 AC: 141620 AN: 1111806

Other (OTH) AF: 0.112 AC: 6757 AN: 60382

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

African (AFR) AF: 0.0221 AC: 914 AN: 41418

American (AMR) AF: 0.100 AC: 1527 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0847 AC: 406 AN: 4792

European-Finnish (FIN) AF: 0.126 AC: 1328 AN: 10506

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8811 AN: 67958

Other (OTH) AF: 0.117 AC: 244 AN: 2090

Alfa AF: 0.108 Hom.: 820

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

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 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
PhyloP100		0.35
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17481856; hg19: chr5-96116808;