rs13186739

Positions:

• chr5-96785539-C-T

Variant summary

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

The NM_001040458.3(ERAP1):​c.1943+249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 482,464 control chromosomes in the GnomAD database, including 7,591 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 0.16 (2272 hom., cov: 32)
  • Exomes 𝑓: 0.17 (5319 hom.)
• Consequence: ERAP1 NM_001040458.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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]

LOC124901031 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1943+249G>A		intron_variant		ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1943+249G>A		intron_variant		1	NM_001040458.3	ENSP00000406304.2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24624 AN: 151940 Hom.: 2270 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.168 AC: 55662 AN: 330406 Hom.: 5319 Cov.: 3 AF XY: 0.163 AC XY: 28807 AN XY: 177156

Gnomad4 AFR exome AF: 0.0935

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.0429

Gnomad4 SAS exome AF: 0.0960

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.162 AC: 24641 AN: 152058 Hom.: 2272 Cov.: 32 AF XY: 0.160 AC XY: 11867 AN XY: 74332

Gnomad4 AFR AF: 0.0964

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0470

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.138

Alfa AF: 0.188 Hom.: 316

Bravo AF: 0.155

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.61

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: rs13186739; hg19: chr5-96121243;