dbSNP rs469758: ERAP1:c.1760-40G>A (chr5-96786011-C-T) – 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.1760-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,593,676 control chromosomes in the GnomAD database, including 331,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 29780 hom., cov: 32)

Exomes 𝑓: 0.65 ( 301809 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.131

Publications

27 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-96786011-C-T is Benign according to our data. Variant chr5-96786011-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688356.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3 link	c.1760-40G>A		intron_variant	Intron 12 of 18	ENST00000443439.7	NP_001035548.1	Q9NZ08-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP1	ENST00000443439.7 link	c.1760-40G>A		intron_variant	Intron 12 of 18	1	NM_001040458.3	ENSP00000406304.2		Q9NZ08-1

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94786

AN:

151970

Hom.:

29750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.565

GnomAD2 exomes

AF:

0.620

AC:

151933

AN:

244978

AF XY:

0.621

show subpopulations

Gnomad AFR exome

AF:

0.609

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.553

Gnomad EAS exome

AF:

0.482

Gnomad FIN exome

AF:

0.655

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.645

AC:

930518

AN:

1441588

Hom.:

301809

Cov.:

AF XY:

0.644

AC XY:

462599

AN XY:

718260

show subpopulations

African (AFR)

AF:

0.596

AC:

19712

AN:

33056

American (AMR)

AF:

0.609

AC:

27036

AN:

44416

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

14437

AN:

26024

East Asian (EAS)

AF:

0.515

AC:

20378

AN:

39538

South Asian (SAS)

AF:

0.587

AC:

50265

AN:

85660

European-Finnish (FIN)

AF:

0.653

AC:

33404

AN:

51174

Middle Eastern (MID)

AF:

0.594

AC:

3408

AN:

5742

European-Non Finnish (NFE)

AF:

0.661

AC:

724670

AN:

1096248

Other (OTH)

AF:

0.623

AC:

37208

AN:

59730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

16220

32440

48661

64881

81101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18738

37476

56214

74952

93690

<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:

0.624

AC:

94862

AN:

152088

Hom.:

29780

Cov.:

AF XY:

0.621

AC XY:

46163

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.603

AC:

25009

AN:

41458

American (AMR)

AF:

0.596

AC:

9111

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1939

AN:

3472

East Asian (EAS)

AF:

0.514

AC:

2658

AN:

5176

South Asian (SAS)

AF:

0.588

AC:

2833

AN:

4818

European-Finnish (FIN)

AF:

0.646

AC:

6825

AN:

10558

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.658

AC:

44735

AN:

68002

Other (OTH)

AF:

0.566

AC:

1193

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1886

3772

5657

7543

9429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.632

Hom.:

6366

Bravo

AF:

0.616

Asia WGS

AF:

0.592

AC:

2061

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 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.7

(source)

DANN

Benign

0.43

PhyloP100

0.13

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