5-96783569-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.2101-334T>C		intron_variant	Intron 14 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.2101-334T>C		intron_variant	Intron 14 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.2101-334T>C		intron_variant	Intron 14 of 19	1		ENSP00000296754.3
ERAP1	ENST00000514604.5	n.525-334T>C		intron_variant	Intron 4 of 5	5

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

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.669

Alfa AF: 0.643 Hom.: 1867

Bravo AF: 0.698

Asia WGS AF: 0.678 AC: 2358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs27432; hg19: chr5-96119273;