dbSNP rs1065407: ERAP1:c.*17A>T (chr5-96776379-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040458.3(ERAP1):c.*17A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,599,370 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ERAP1
NM_001040458.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.952

Publications

47 publications found

Variant links:

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]

ERAP1 links:

CAST (HGNC:):

CAST links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3 link	c.*17A>T		3_prime_UTR_variant	Exon 19 of 19	ENST00000443439.7	NP_001035548.1	Q9NZ08-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ERAP1	ENST00000443439.7 link	c.*17A>T	3_prime_UTR_variant	Exon 19 of 19	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 link	c.2818+25A>T	intron_variant	Intron 19 of 19	1		ENSP00000296754.3	Q9NZ08-2
CAST	ENST00000510098.1 link	n.*351-489T>A	intron_variant	Intron 10 of 11	1		ENSP00000427195.1	A0A0C4DGD1
ERAP1	ENST00000512852.1 link	c.352+25A>T	intron_variant	Intron 3 of 3	3		ENSP00000425381.1	H0Y9X5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000328

AC:

AN:

243868

AF XY:

0.0000380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000359

AC:

AN:

1447256

Hom.:

Cov.:

AF XY:

0.0000362

AC XY:

AN XY:

717916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32718

American (AMR)

AF:

0.000117

AC:

AN:

42708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25706

East Asian (EAS)

AF:

0.00

AC:

AN:

39442

South Asian (SAS)

AF:

0.00

AC:

AN:

83884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.0000417

AC:

AN:

1104336

Other (OTH)

AF:

0.0000167

AC:

AN:

59776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.000196

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

20782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

(source)

DANN

Benign

0.76

PhyloP100

-0.95

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

Publications

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rs1065407

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over