dbSNP rs27043: ERAP1:c.2447+97C>T (chr5-96781596-G-A) – 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.2447+97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,491,934 control chromosomes in the GnomAD database, including 514,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.80 ( 48588 hom., cov: 31)

Exomes 𝑓: 0.83 ( 466217 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.207

Publications

19 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:

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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=-0.66).

BP6

Variant 5-96781596-G-A is Benign according to our data. Variant chr5-96781596-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688540.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3 link	c.2447+97C>T		intron_variant	Intron 16 of 18	ENST00000443439.7	NP_001035548.1	Q9NZ08-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ERAP1	ENST00000443439.7 link	c.2447+97C>T	intron_variant	Intron 16 of 18	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 link	c.2447+97C>T	intron_variant	Intron 16 of 19	1		ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000514604.5 link	n.*98C>T	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120844

AN:

151996

Hom.:

48544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.765

Gnomad ASJ

AF:

0.824

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:

0.787

GnomAD4 exome

AF:

0.832

AC:

1114529

AN:

1339820

Hom.:

466217

AF XY:

0.833

AC XY:

560637

AN XY:

673118

show subpopulations

African (AFR)

AF:

0.732

AC:

22739

AN:

31072

American (AMR)

AF:

0.735

AC:

32670

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.825

AC:

20996

AN:

25464

East Asian (EAS)

AF:

0.562

AC:

21950

AN:

39090

South Asian (SAS)

AF:

0.800

AC:

66527

AN:

83124

European-Finnish (FIN)

AF:

0.814

AC:

37956

AN:

46650

Middle Eastern (MID)

AF:

0.840

AC:

4652

AN:

5536

European-Non Finnish (NFE)

AF:

0.854

AC:

860933

AN:

1007962

Other (OTH)

AF:

0.816

AC:

46106

AN:

56468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

9649

19298

28946

38595

48244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18390

36780

55170

73560

91950

<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:

120940

AN:

152114

Hom.:

48588

Cov.:

AF XY:

0.793

AC XY:

58939

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.733

AC:

30406

AN:

41468

American (AMR)

AF:

0.765

AC:

11696

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2861

AN:

3470

East Asian (EAS)

AF:

0.545

AC:

2806

AN:

5150

South Asian (SAS)

AF:

0.806

AC:

3888

AN:

4822

European-Finnish (FIN)

AF:

0.812

AC:

8606

AN:

10596

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.853

AC:

57981

AN:

68008

Other (OTH)

AF:

0.787

AC:

1663

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1233

2466

3698

4931

6164

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:

0.827

Hom.:

12289

Bravo

AF:

0.785

Asia WGS

AF:

0.711

AC:

2474

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.3

(source)

DANN

Benign

0.68

PhyloP100

-0.21

PromoterAI

-0.042

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over