5-96783569-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040458.3(ERAP1):​c.2101-334T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,050 control chromosomes in the GnomAD database, including 37,832 homozygotes. 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 0.70 (37832 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	NM_001040458.3	MANE Select	c.2101-334T>C		intron	N/A	NP_001035548.1	Q9NZ08-1
	ERAP1	NM_001349244.2		c.2101-334T>C		intron	N/A	NP_001336173.1	Q9NZ08-2
	ERAP1	NM_016442.5		c.2101-334T>C		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>C		intron	N/A	ENSP00000406304.2	Q9NZ08-1
	ERAP1	ENST00000296754.7	TSL:1	c.2101-334T>C		intron	N/A	ENSP00000296754.3	Q9NZ08-2
	ERAP1	ENST00000853356.1		c.2101-334T>C		intron	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106811 AN: 151932 Hom.: 37784 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.703 AC: 106911 AN: 152050 Hom.: 37832 Cov.: 32 AF XY: 0.700 AC XY: 52048 AN XY: 74310

African (AFR) AF: 0.711 AC: 29460 AN: 41458

American (AMR) AF: 0.662 AC: 10115 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2428 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2811 AN: 5164

South Asian (SAS) AF: 0.722 AC: 3482 AN: 4824

European-Finnish (FIN) AF: 0.685 AC: 7237 AN: 10560

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49136 AN: 67978

Other (OTH) AF: 0.669 AC: 1412 AN: 2110

Alfa AF: 0.649 Hom.: 2068

Bravo AF: 0.698

Asia WGS AF: 0.678 AC: 2358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.024
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;