chr5-96781596-G-A

Variant names:

• chr5-96781596-G-A
• rs27043
• NM_001040458.3:c.2447+97C>T

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.2447+97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,491,934 control chromosomes in the GnomAD database, including 514,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (48588 hom., cov: 31)
  • Exomes 𝑓: 0.83 (466217 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.207
• Publications: 19 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 5-96781596-G-A is Benign according to our data. Variant chr5-96781596-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	NM_001040458.3	MANE Select	c.2447+97C>T		intron	N/A	NP_001035548.1
	ERAP1	NM_001349244.2		c.2447+97C>T		intron	N/A	NP_001336173.1
	ERAP1	NM_016442.5		c.2447+97C>T		intron	N/A	NP_057526.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.2447+97C>T		intron	N/A	ENSP00000406304.2
	ERAP1	ENST00000296754.7	TSL:1	c.2447+97C>T		intron	N/A	ENSP00000296754.3
	ERAP1	ENST00000514604.5	TSL:5	n.*98C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120844 AN: 151996 Hom.: 48544 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.832 AC: 1114529 AN: 1339820 Hom.: 466217 AF XY: 0.833 AC XY: 560637 AN XY: 673118

African (AFR) AF: 0.732 AC: 22739 AN: 31072

American (AMR) AF: 0.735 AC: 32670 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 20996 AN: 25464

East Asian (EAS) AF: 0.562 AC: 21950 AN: 39090

South Asian (SAS) AF: 0.800 AC: 66527 AN: 83124

European-Finnish (FIN) AF: 0.814 AC: 37956 AN: 46650

Middle Eastern (MID) AF: 0.840 AC: 4652 AN: 5536

European-Non Finnish (NFE) AF: 0.854 AC: 860933 AN: 1007962

Other (OTH) AF: 0.816 AC: 46106 AN: 56468

GnomAD4 genome AF: 0.795 AC: 120940 AN: 152114 Hom.: 48588 Cov.: 31 AF XY: 0.793 AC XY: 58939 AN XY: 74366

African (AFR) AF: 0.733 AC: 30406 AN: 41468

American (AMR) AF: 0.765 AC: 11696 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2861 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2806 AN: 5150

South Asian (SAS) AF: 0.806 AC: 3888 AN: 4822

European-Finnish (FIN) AF: 0.812 AC: 8606 AN: 10596

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 57981 AN: 68008

Other (OTH) AF: 0.787 AC: 1663 AN: 2112

Alfa AF: 0.827 Hom.: 12289

Bravo AF: 0.785

Asia WGS AF: 0.711 AC: 2474 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 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.3
DANN	Benign	0.68
PhyloP100		-0.21
PromoterAI		-0.042	Neutral
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: rs27043; hg19: chr5-96117300; COSMIC: COSV57088400; COSMIC: COSV57088400;