dbSNP rs42398: ERAP1:c.1944-671G>A (chr5-96784751-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.1944-671G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,668 control chromosomes in the GnomAD database, including 48,727 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 0.79 ( 48537 hom., cov: 31)

Exomes 𝑓: 0.79 ( 190 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

25 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:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 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.1944-671G>A	intron	N/A	NP_001035548.1	Q9NZ08-1
ERAP1	NM_001349244.2		c.1944-671G>A	intron	N/A	NP_001336173.1	Q9NZ08-2
ERAP1	NM_016442.5		c.1944-671G>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.1944-671G>A	intron	N/A	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7	TSL:1	c.1944-671G>A	intron	N/A	ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000853356.1		c.1944-671G>A	intron	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120760

AN:

151948

Hom.:

48492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.880

Gnomad AMR

AF:

0.765

Gnomad ASJ

AF:

0.825

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.853

Gnomad OTH

AF:

0.786

GnomAD4 exome

AF:

0.792

AC:

475

AN:

600

Hom.:

190

Cov.:

AF XY:

0.803

AC XY:

252

AN XY:

314

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.622

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AF:

0.708

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.825

AC:

381

AN:

462

Other (OTH)

AF:

0.808

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.795

AC:

120856

AN:

152068

Hom.:

48537

Cov.:

AF XY:

0.792

AC XY:

58896

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.732

AC:

30330

AN:

41432

American (AMR)

AF:

0.765

AC:

11684

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.825

AC:

2863

AN:

3472

East Asian (EAS)

AF:

0.544

AC:

2814

AN:

5170

South Asian (SAS)

AF:

0.806

AC:

3888

AN:

4822

European-Finnish (FIN)

AF:

0.812

AC:

8593

AN:

10582

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.853

AC:

57989

AN:

68004

Other (OTH)

AF:

0.787

AC:

1659

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1200

2399

3599

4798

5998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.829

Hom.:

164460

Bravo

AF:

0.785

Asia WGS

AF:

0.712

AC:

2478

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.11

(source)

DANN

Benign

0.18

PhyloP100

-1.0

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