dbSNP rs27528: ERAP1:c.663+40A>G (chr5-96800822-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001040458.3(ERAP1):c.663+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,609,316 control chromosomes in the GnomAD database, including 51,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5058 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46856 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.290

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-96800822-T-C is Benign according to our data. Variant chr5-96800822-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688414.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 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.663+40A>G	intron	N/A	NP_001035548.1	Q9NZ08-1
ERAP1	NM_001349244.2		c.663+40A>G	intron	N/A	NP_001336173.1	Q9NZ08-2
ERAP1	NM_016442.5		c.663+40A>G	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.663+40A>G	intron	N/A	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7	TSL:1	c.663+40A>G	intron	N/A	ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000853356.1		c.663+40A>G	intron	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38642

AN:

152050

Hom.:

5051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.244

GnomAD2 exomes

AF:

0.272

AC:

68198

AN:

251024

AF XY:

0.268

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.413

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.247

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.251

AC:

365656

AN:

1457148

Hom.:

46856

Cov.:

AF XY:

0.252

AC XY:

182499

AN XY:

725208

show subpopulations

African (AFR)

AF:

0.247

AC:

8233

AN:

33390

American (AMR)

AF:

0.403

AC:

18027

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

6632

AN:

26104

East Asian (EAS)

AF:

0.210

AC:

8337

AN:

39646

South Asian (SAS)

AF:

0.282

AC:

24256

AN:

86146

European-Finnish (FIN)

AF:

0.273

AC:

14571

AN:

53350

Middle Eastern (MID)

AF:

0.233

AC:

1339

AN:

5758

European-Non Finnish (NFE)

AF:

0.243

AC:

269241

AN:

1107832

Other (OTH)

AF:

0.249

AC:

15020

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

13687

27373

41060

54746

68433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9318

18636

27954

37272

46590

<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:

0.254

AC:

38675

AN:

152168

Hom.:

5058

Cov.:

AF XY:

0.258

AC XY:

19181

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.245

AC:

10182

AN:

41514

American (AMR)

AF:

0.325

AC:

4969

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

904

AN:

3468

East Asian (EAS)

AF:

0.195

AC:

1008

AN:

5176

South Asian (SAS)

AF:

0.295

AC:

1422

AN:

4820

European-Finnish (FIN)

AF:

0.280

AC:

2958

AN:

10578

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16466

AN:

68010

Other (OTH)

AF:

0.241

AC:

510

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1493

2987

4480

5974

7467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.252

Hom.:

907

Bravo

AF:

0.259

Asia WGS

AF:

0.232

AC:

812

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.021

(source)

DANN

Benign

0.43

PhyloP100

-0.29

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