5-96783569-A-C

Variant names:

• chr5-96783569-A-C
• rs27432
• NM_001040458.3:c.2101-334T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040458.3(ERAP1):​c.2101-334T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 151,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00012 (0 hom., cov: 32)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 39 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.2101-334T>G		intron	N/A	NP_001035548.1	Q9NZ08-1
	ERAP1	NM_001349244.2		c.2101-334T>G		intron	N/A	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.2101-334T>G		intron	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.2101-334T>G		intron	N/A	ENSP00000406304.2	Q9NZ08-1
	ERAP1	ENST00000296754.7	TSL:1	c.2101-334T>G		intron	N/A	ENSP00000296754.3	Q9NZ08-2
	ERAP1	ENST00000853356.1		c.2101-334T>G		intron	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 151986 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000479

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

GnomAD4 genome AF: 0.000118 AC: 18 AN: 151986 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74214

African (AFR) AF: 0.0000242 AC: 1 AN: 41356

American (AMR) AF: 0.000459 AC: 7 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67996

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00 Hom.: 2068

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.8
DANN	Benign	0.78
PhyloP100		0.024
Mutation Taster		=100/0	polymorphism

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: rs27432; hg19: chr5-96119273;