5-96776379-T-G

Variant names:

• chr5-96776379-T-G
• rs1065407
• NM_001040458.3:c.*17A>C

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.*17A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,599,214 control chromosomes in the GnomAD database, including 85,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5849 hom., cov: 32)
  • Exomes 𝑓: 0.32 (79945 hom.)
• Consequence: ERAP1 NM_001040458.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.952
• Publications: 47 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]

CAST (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-96776379-T-G is Benign according to our data. Variant chr5-96776379-T-G is described in ClinVar as [Benign]. Clinvar id is 2688446.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.*17A>C		3_prime_UTR_variant	Exon 19 of 19	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.*17A>C		3_prime_UTR_variant	Exon 19 of 19	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.2818+25A>C		intron_variant	Intron 19 of 19	1		ENSP00000296754.3
CAST	ENST00000510098.1	n.*351-489T>G		intron_variant	Intron 10 of 11	1		ENSP00000427195.1
ERAP1	ENST00000512852.1	c.352+25A>C		intron_variant	Intron 3 of 3	3		ENSP00000425381.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39206 AN: 152064 Hom.: 5842 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.262 AC: 64000 AN: 243868 AF XY: 0.269

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.0568

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.323 AC: 467042 AN: 1447032 Hom.: 79945 Cov.: 36 AF XY: 0.321 AC XY: 230451 AN XY: 717808

African (AFR) AF: 0.125 AC: 4094 AN: 32710

American (AMR) AF: 0.164 AC: 7005 AN: 42702

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 9545 AN: 25698

East Asian (EAS) AF: 0.0520 AC: 2051 AN: 39424

South Asian (SAS) AF: 0.210 AC: 17624 AN: 83872

European-Finnish (FIN) AF: 0.283 AC: 14984 AN: 52982

Middle Eastern (MID) AF: 0.356 AC: 2025 AN: 5684

European-Non Finnish (NFE) AF: 0.355 AC: 391451 AN: 1104194

Other (OTH) AF: 0.306 AC: 18263 AN: 59766

GnomAD4 genome AF: 0.258 AC: 39219 AN: 152182 Hom.: 5849 Cov.: 32 AF XY: 0.252 AC XY: 18725 AN XY: 74402

African (AFR) AF: 0.130 AC: 5399 AN: 41548

American (AMR) AF: 0.229 AC: 3495 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1278 AN: 3466

East Asian (EAS) AF: 0.0559 AC: 290 AN: 5186

South Asian (SAS) AF: 0.196 AC: 947 AN: 4826

European-Finnish (FIN) AF: 0.288 AC: 3051 AN: 10592

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.350 AC: 23791 AN: 67962

Other (OTH) AF: 0.267 AC: 563 AN: 2110

Alfa AF: 0.306 Hom.: 20782

Bravo AF: 0.248

Asia WGS AF: 0.152 AC: 528 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 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-0.95
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: rs1065407; hg19: chr5-96112083; COSMIC: COSV57085221; COSMIC: COSV57085221;