rs30333

Positions:

• chr5-96798532-G-A
• chr5-96798532-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040458.3(ERAP1):​c.664-1223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 151,528 control chromosomes in the GnomAD database, including 1,754 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 0.14 (1754 hom., cov: 30)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERAP1	NM_001040458.3	c.664-1223C>T		intron_variant		ENST00000443439.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP1	ENST00000443439.7	c.664-1223C>T		intron_variant		1	NM_001040458.3	P1
ERAP1	ENST00000296754.7	c.664-1223C>T		intron_variant		1
ERAP1	ENST00000503921.5	c.-60-1223C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21703 AN: 151414 Hom.: 1748 Cov.: 30

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.143 AC: 21735 AN: 151528 Hom.: 1754 Cov.: 30 AF XY: 0.144 AC XY: 10652 AN XY: 73990

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.106

Alfa AF: 0.106 Hom.: 1174

Bravo AF: 0.147

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs30333; hg19: chr5-96134235; COSMIC: COSV57086435; COSMIC: COSV57086435;