rs27434

Variant names:

• chr5-96793809-A-G
• rs27434
• NM_001040458.3:c.1068T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-96793809-A-G
• chr5-96793809-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001040458.3(ERAP1):​c.1068T>C​(p.Ala356Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,610,604 control chromosomes in the GnomAD database, including 466,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39082 hom., cov: 32)
  • Exomes 𝑓: 0.76 (426935 hom.)
• Consequence: ERAP1 NM_001040458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.208
• Publications: 109 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-96793809-A-G is Benign according to our data. Variant chr5-96793809-A-G is described in ClinVar as Benign. ClinVar VariationId is 1287401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.208 with no splicing effect.
• 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.1068T>C	p.Ala356Ala	synonymous_variant	Exon 6 of 19	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1068T>C	p.Ala356Ala	synonymous_variant	Exon 6 of 19	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.1068T>C	p.Ala356Ala	synonymous_variant	Exon 6 of 20	1		ENSP00000296754.3
ERAP1	ENST00000503311.1	n.-138T>C		upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108048 AN: 151902 Hom.: 39054 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.684

GnomAD2 exomes AF: 0.718 AC: 179728 AN: 250182 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: 0.481

Gnomad FIN exome AF: 0.772

Gnomad NFE exome AF: 0.788

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.762 AC: 1111593 AN: 1458584 Hom.: 426935 Cov.: 39 AF XY: 0.761 AC XY: 552100 AN XY: 725640

African (AFR) AF: 0.602 AC: 20107 AN: 33376

American (AMR) AF: 0.685 AC: 30560 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17915 AN: 26100

East Asian (EAS) AF: 0.516 AC: 20446 AN: 39650

South Asian (SAS) AF: 0.668 AC: 57602 AN: 86176

European-Finnish (FIN) AF: 0.771 AC: 41167 AN: 53378

Middle Eastern (MID) AF: 0.707 AC: 4066 AN: 5754

European-Non Finnish (NFE) AF: 0.789 AC: 875453 AN: 1109266

Other (OTH) AF: 0.735 AC: 44277 AN: 60252

GnomAD4 genome AF: 0.711 AC: 108119 AN: 152020 Hom.: 39082 Cov.: 32 AF XY: 0.709 AC XY: 52666 AN XY: 74298

African (AFR) AF: 0.609 AC: 25257 AN: 41450

American (AMR) AF: 0.697 AC: 10647 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2385 AN: 3466

East Asian (EAS) AF: 0.515 AC: 2657 AN: 5160

South Asian (SAS) AF: 0.672 AC: 3229 AN: 4806

European-Finnish (FIN) AF: 0.773 AC: 8170 AN: 10572

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

European-Non Finnish (NFE) AF: 0.788 AC: 53565 AN: 67978

Other (OTH) AF: 0.684 AC: 1445 AN: 2112

Alfa AF: 0.754 Hom.: 196597

Bravo AF: 0.699

Asia WGS AF: 0.626 AC: 2179 AN: 3478

EpiCase AF: 0.784

EpiControl AF: 0.774

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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. -

not provided Benign:1

Feb 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23818875, 19692350, 30272298, 20062062) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.8
DANN	Benign	0.46
PhyloP100		-0.21
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs27434; hg19: chr5-96129512; COSMIC: COSV57085707; COSMIC: COSV57085707;