5-96803546-AC-GA

Variant names:

• chr5-96803546-AC-GA
• NM_001040458.3:c.380_381delGTinsTC
• ERAP1 p.Arg127Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001040458.3(ERAP1):​c.380_381delGTinsTC​(p.Arg127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R127P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ERAP1 NM_001040458.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 0 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]

ENSG00000272109 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	NM_001040458.3	MANE Select	c.380_381delGTinsTC	p.Arg127Leu	missense	N/A	NP_001035548.1	Q9NZ08-1
	ERAP1	NM_001349244.2		c.380_381delGTinsTC	p.Arg127Leu	missense	N/A	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.380_381delGTinsTC	p.Arg127Leu	missense	N/A	NP_057526.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.380_381delGTinsTC	p.Arg127Leu	missense	N/A	ENSP00000406304.2	Q9NZ08-1
	ERAP1	ENST00000296754.7	TSL:1	c.380_381delGTinsTC	p.Arg127Leu	missense	N/A	ENSP00000296754.3	Q9NZ08-2
	ERAP1	ENST00000853356.1		c.380_381delGTinsTC	p.Arg127Leu	missense	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-96139249;