rs18036

Positions:

• chr5-96819905-T-C

Variant summary

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

The XM_011543484.3(ERAP1):​c.-267+3032A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,142 control chromosomes in the GnomAD database, including 4,184 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 0.23 (4184 hom., cov: 32)
• Consequence: ERAP1 XM_011543484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

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]

ENSG00000247121 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	XM_011543484.3	c.-267+3032A>G		intron_variant			XP_011541786.1
ERAP1	XM_011543485.3	c.-270-5595A>G		intron_variant			XP_011541787.1
ERAP1	XM_017009581.2	c.-271+3032A>G		intron_variant			XP_016865070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000247121	ENST00000501338.5	n.1962+3032A>G		intron_variant		2
ENSG00000247121	ENST00000502262.4	n.433+3032A>G		intron_variant		5
ENSG00000247121	ENST00000504056.5	n.192-5595A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35336 AN: 152024 Hom.: 4179 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.232 AC: 35360 AN: 152142 Hom.: 4184 Cov.: 32 AF XY: 0.232 AC XY: 17268 AN XY: 74364

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.240

Alfa AF: 0.239 Hom.: 8943

Bravo AF: 0.224

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs18036; hg19: chr5-96155608;