rs3213809

Variant names:

• chr5-96792130-G-A
• rs3213809
• NM_001040458.3:c.1251C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-96792130-G-A
• chr5-96792130-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001040458.3(ERAP1):​c.1251C>T​(p.His417His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,472 control chromosomes in the GnomAD database, including 14,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1232 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13156 hom.)
• Consequence: ERAP1 NM_001040458.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.600
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 5-96792130-G-A is Benign according to our data. Variant chr5-96792130-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1251C>T	p.His417His	synonymous_variant	Exon 8 of 19	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1251C>T	p.His417His	synonymous_variant	Exon 8 of 19	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.1251C>T	p.His417His	synonymous_variant	Exon 8 of 20	1		ENSP00000296754.3
ERAP1	ENST00000503311.1	n.335C>T		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16905 AN: 152048 Hom.: 1232 Cov.: 33

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.135 AC: 33966 AN: 251366 AF XY: 0.134

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.0284

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.131 AC: 190774 AN: 1461304 Hom.: 13156 Cov.: 31 AF XY: 0.131 AC XY: 95046 AN XY: 726968

African (AFR) AF: 0.0287 AC: 962 AN: 33478

American (AMR) AF: 0.224 AC: 10008 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3404 AN: 26132

East Asian (EAS) AF: 0.0302 AC: 1199 AN: 39656

South Asian (SAS) AF: 0.120 AC: 10337 AN: 86234

European-Finnish (FIN) AF: 0.141 AC: 7523 AN: 53410

Middle Eastern (MID) AF: 0.123 AC: 707 AN: 5766

European-Non Finnish (NFE) AF: 0.134 AC: 148985 AN: 1111534

Other (OTH) AF: 0.127 AC: 7649 AN: 60372

GnomAD4 genome AF: 0.111 AC: 16906 AN: 152168 Hom.: 1232 Cov.: 33 AF XY: 0.114 AC XY: 8476 AN XY: 74386

African (AFR) AF: 0.0313 AC: 1299 AN: 41530

American (AMR) AF: 0.198 AC: 3028 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3466

East Asian (EAS) AF: 0.0301 AC: 156 AN: 5180

South Asian (SAS) AF: 0.126 AC: 609 AN: 4820

European-Finnish (FIN) AF: 0.147 AC: 1555 AN: 10568

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

European-Non Finnish (NFE) AF: 0.137 AC: 9322 AN: 68002

Other (OTH) AF: 0.136 AC: 287 AN: 2110

Alfa AF: 0.123 Hom.: 2610

Bravo AF: 0.112

Asia WGS AF: 0.0700 AC: 245 AN: 3478

EpiCase AF: 0.138

EpiControl AF: 0.140

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 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 36. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.6
DANN	Benign	0.69
PhyloP100		0.60
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: rs3213809; hg19: chr5-96127833;