chr5-96798532-G-A

Variant names:

• chr5-96798532-G-A
• rs30333
• NM_001040458.3:c.664-1223C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.9).
• 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 rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.664-1223C>T		intron_variant	Intron 3 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.664-1223C>T		intron_variant	Intron 3 of 18	1	NM_001040458.3	ENSP00000406304.2
ERAP1	ENST00000296754.7	c.664-1223C>T		intron_variant	Intron 3 of 19	1		ENSP00000296754.3
ERAP1	ENST00000503921.5	c.-60-1223C>T		intron_variant	Intron 2 of 2	4		ENSP00000427025.1

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

African (AFR) AF: 0.216 AC: 8903 AN: 41260

American (AMR) AF: 0.127 AC: 1940 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3466

East Asian (EAS) AF: 0.164 AC: 842 AN: 5142

South Asian (SAS) AF: 0.168 AC: 802 AN: 4784

European-Finnish (FIN) AF: 0.131 AC: 1367 AN: 10426

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7151 AN: 67888

Other (OTH) AF: 0.106 AC: 223 AN: 2100

Alfa AF: 0.111 Hom.: 1705

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
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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