dbSNP rs13160562: ERAP1:c.*729C>T (chr5-96775667-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001040458.3(ERAP1):c.*729C>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 0.254 in 241,920 control chromosomes in the GnomAD database, including 8,782 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 0.22 ( 4344 hom., cov: 33)

Exomes 𝑓: 0.30 ( 4438 hom. )

Consequence

ERAP1
NM_001040458.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.123

Publications

48 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3 link	c.*729C>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.*729C>T	3_prime_UTR_variant	Exon 19 of 19	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 link	c.2818+737C>T	intron_variant	Intron 19 of 19	1		ENSP00000296754.3	Q9NZ08-2
CAST	ENST00000510098.1 link	n.*351-1201G>A	intron_variant	Intron 10 of 11	1		ENSP00000427195.1	A0A0C4DGD1
ERAP1	ENST00000512852.1 link	c.*448C>T	downstream_gene_variant		3		ENSP00000425381.1	H0Y9X5

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34189

AN:

152058

Hom.:

4341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0477

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.302

AC:

27135

AN:

89744

Hom.:

4438

Cov.:

AF XY:

0.301

AC XY:

13117

AN XY:

43522

show subpopulations

African (AFR)

AF:

0.118

AC:

188

AN:

1594

American (AMR)

AF:

0.127

AC:

AN:

110

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

151

AN:

546

East Asian (EAS)

AF:

0.0455

AC:

AN:

396

South Asian (SAS)

AF:

0.177

AC:

293

AN:

1656

European-Finnish (FIN)

AF:

0.423

AC:

AN:

Middle Eastern (MID)

AF:

0.289

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.312

AC:

25636

AN:

82282

Other (OTH)

AF:

0.261

AC:

765

AN:

2930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

927

1854

2782

3709

4636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1144

2288

3432

4576

5720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.225

AC:

34200

AN:

152176

Hom.:

4344

Cov.:

AF XY:

0.220

AC XY:

16354

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.125

AC:

5206

AN:

41530

American (AMR)

AF:

0.186

AC:

2849

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

882

AN:

3466

East Asian (EAS)

AF:

0.0480

AC:

249

AN:

5188

South Asian (SAS)

AF:

0.158

AC:

761

AN:

4828

European-Finnish (FIN)

AF:

0.277

AC:

2930

AN:

10592

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.303

AC:

20618

AN:

67960

Other (OTH)

AF:

0.211

AC:

445

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1336

2672

4007

5343

6679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

6298

Bravo

AF:

0.214

Asia WGS

AF:

0.133

AC:

462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.6

(source)

DANN

Benign

0.80

PhyloP100

-0.12

Mutation Taster

=98/2

polymorphism (auto)

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over