rs27039

Variant names:

• chr5-96778846-G-A
• rs27039
• NM_001040458.3:c.2670+1577C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000443439.7(ERAP1):​c.2670+1577C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,016 control chromosomes in the GnomAD database, including 18,171 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 0.47 (18171 hom., cov: 31)
• Consequence: ERAP1 ENST00000443439.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 21 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]

CAST (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443439.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	NM_001040458.3	MANE Select	c.2670+1577C>T		intron	N/A	NP_001035548.1
	ERAP1	NM_001349244.2		c.2670+1577C>T		intron	N/A	NP_001336173.1
	ERAP1	NM_016442.5		c.2670+1577C>T		intron	N/A	NP_057526.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.2670+1577C>T		intron	N/A	ENSP00000406304.2
	ERAP1	ENST00000296754.7	TSL:1	c.2670+1577C>T		intron	N/A	ENSP00000296754.3
	CAST	ENST00000510098.1	TSL:1	n.*438-476G>A		intron	N/A	ENSP00000427195.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72037 AN: 151898 Hom.: 18164 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.474 AC: 72072 AN: 152016 Hom.: 18171 Cov.: 31 AF XY: 0.475 AC XY: 35285 AN XY: 74288

African (AFR) AF: 0.296 AC: 12287 AN: 41454

American (AMR) AF: 0.553 AC: 8456 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1793 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1745 AN: 5168

South Asian (SAS) AF: 0.479 AC: 2312 AN: 4830

European-Finnish (FIN) AF: 0.569 AC: 6000 AN: 10544

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37980 AN: 67946

Other (OTH) AF: 0.471 AC: 993 AN: 2110

Alfa AF: 0.528 Hom.: 28397

Bravo AF: 0.467

Asia WGS AF: 0.398 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.62
PhyloP100		0.34
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: rs27039; hg19: chr5-96114550; COSMIC: COSV57086336; COSMIC: COSV57086336;