rs13186739

Variant names:

• chr5-96785539-C-T
• rs13186739
• NM_001040458.3:c.1943+249G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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]

LOC124901031 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3	c.1943+249G>A		intron_variant	Intron 13 of 18	ENST00000443439.7	NP_001035548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7	c.1943+249G>A		intron_variant	Intron 13 of 18	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

African (AFR) AF: 0.0935 AC: 904 AN: 9672

American (AMR) AF: 0.110 AC: 1705 AN: 15500

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 1225 AN: 9946

East Asian (EAS) AF: 0.0429 AC: 833 AN: 19406

South Asian (SAS) AF: 0.0960 AC: 4223 AN: 43980

European-Finnish (FIN) AF: 0.184 AC: 3012 AN: 16394

Middle Eastern (MID) AF: 0.114 AC: 158 AN: 1382

European-Non Finnish (NFE) AF: 0.207 AC: 40541 AN: 195562

Other (OTH) AF: 0.165 AC: 3061 AN: 18564

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

African (AFR) AF: 0.0964 AC: 4000 AN: 41492

American (AMR) AF: 0.139 AC: 2123 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3472

East Asian (EAS) AF: 0.0470 AC: 243 AN: 5174

South Asian (SAS) AF: 0.0918 AC: 442 AN: 4814

European-Finnish (FIN) AF: 0.204 AC: 2151 AN: 10542

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14820 AN: 67982

Other (OTH) AF: 0.138 AC: 291 AN: 2110

Alfa AF: 0.186 Hom.: 321

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
PhyloP100		0.26
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13186739; hg19: chr5-96121243;