Genetic Variant ERAP1:c.1680-205G>A (chr5-96786754-C-T) – 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.1680-205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 549,760 control chromosomes in the GnomAD database, including 8,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2259 hom., cov: 32)

Exomes 𝑓: 0.17 ( 6107 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

16 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:

LOC124901031 (HGNC:):

LOC124901031 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040458.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERAP1	NM_001040458.3	MANE Select	c.1680-205G>A	intron	N/A	NP_001035548.1	Q9NZ08-1
ERAP1	NM_001349244.2		c.1680-205G>A	intron	N/A	NP_001336173.1	Q9NZ08-2
ERAP1	NM_016442.5		c.1680-205G>A	intron	N/A	NP_057526.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERAP1	ENST00000443439.7	TSL:1 MANE Select	c.1680-205G>A	intron	N/A	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7	TSL:1	c.1680-205G>A	intron	N/A	ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000853356.1		c.1680-205G>A	intron	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24534

AN:

151984

Hom.:

2257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0949

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.0463

Gnomad SAS

AF:

0.0905

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.165

AC:

65801

AN:

397658

Hom.:

6107

Cov.:

AF XY:

0.161

AC XY:

34216

AN XY:

212056

show subpopulations

African (AFR)

AF:

0.0908

AC:

1018

AN:

11206

American (AMR)

AF:

0.108

AC:

1809

AN:

16812

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

1426

AN:

11958

East Asian (EAS)

AF:

0.0421

AC:

1142

AN:

27128

South Asian (SAS)

AF:

0.0950

AC:

4167

AN:

43882

European-Finnish (FIN)

AF:

0.178

AC:

4340

AN:

24366

Middle Eastern (MID)

AF:

0.112

AC:

192

AN:

1720

European-Non Finnish (NFE)

AF:

0.202

AC:

48026

AN:

237884

Other (OTH)

AF:

0.162

AC:

3681

AN:

22702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

2210

4420

6630

8840

11050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<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:

0.161

AC:

24550

AN:

152102

Hom.:

2259

Cov.:

AF XY:

0.159

AC XY:

11818

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0948

AC:

3935

AN:

41510

American (AMR)

AF:

0.139

AC:

2122

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

433

AN:

3464

East Asian (EAS)

AF:

0.0466

AC:

241

AN:

5176

South Asian (SAS)

AF:

0.0914

AC:

440

AN:

4814

European-Finnish (FIN)

AF:

0.204

AC:

2150

AN:

10560

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14802

AN:

67974

Other (OTH)

AF:

0.136

AC:

288

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1033

2067

3100

4134

5167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.192

Hom.:

1513

Bravo

AF:

0.154

Asia WGS

AF:

0.0920

AC:

320

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.6

(source)

DANN

Benign

0.69

PhyloP100

0.085

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over