dbSNP rs27710: ERAP1:c.1452+18T>C (chr5-96790494-A-G) – 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.1452+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,612,748 control chromosomes in the GnomAD database, including 336,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 29851 hom., cov: 32)

Exomes 𝑓: 0.65 ( 306196 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.281

Publications

30 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=-0.79).

BP6

Variant 5-96790494-A-G is Benign according to our data. Variant chr5-96790494-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688361.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.

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.1452+18T>C	intron	N/A	NP_001035548.1	Q9NZ08-1
ERAP1	NM_001349244.2		c.1452+18T>C	intron	N/A	NP_001336173.1	Q9NZ08-2
ERAP1	NM_016442.5		c.1452+18T>C	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.1452+18T>C	intron	N/A	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7	TSL:1	c.1452+18T>C	intron	N/A	ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000853356.1		c.1452+18T>C	intron	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94888

AN:

151968

Hom.:

29820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.596

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.567

GnomAD2 exomes

AF:

0.620

AC:

155517

AN:

250896

AF XY:

0.620

show subpopulations

Gnomad AFR exome

AF:

0.607

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.480

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.616

GnomAD4 exome

AF:

0.646

AC:

943257

AN:

1460662

Hom.:

306196

Cov.:

AF XY:

0.644

AC XY:

468243

AN XY:

726698

show subpopulations

African (AFR)

AF:

0.598

AC:

20018

AN:

33462

American (AMR)

AF:

0.608

AC:

27207

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

14591

AN:

26126

East Asian (EAS)

AF:

0.515

AC:

20425

AN:

39652

South Asian (SAS)

AF:

0.586

AC:

50553

AN:

86232

European-Finnish (FIN)

AF:

0.653

AC:

34711

AN:

53166

Middle Eastern (MID)

AF:

0.594

AC:

3425

AN:

5764

European-Non Finnish (NFE)

AF:

0.661

AC:

734692

AN:

1111156

Other (OTH)

AF:

0.623

AC:

37635

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

18491

36982

55472

73963

92454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19076

38152

57228

76304

95380

<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:

94965

AN:

152086

Hom.:

29851

Cov.:

AF XY:

0.622

AC XY:

46205

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.605

AC:

25060

AN:

41452

American (AMR)

AF:

0.596

AC:

9113

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

1950

AN:

3470

East Asian (EAS)

AF:

0.515

AC:

2661

AN:

5172

South Asian (SAS)

AF:

0.587

AC:

2830

AN:

4822

European-Finnish (FIN)

AF:

0.646

AC:

6841

AN:

10584

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.658

AC:

44750

AN:

67982

Other (OTH)

AF:

0.569

AC:

1203

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1840

3679

5519

7358

9198

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.:

7757

Bravo

AF:

0.617

Asia WGS

AF:

0.592

AC:

2060

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

-0.79

CADD

Benign

7.3

(source)

DANN

Benign

0.76

PhyloP100

0.28

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