dbSNP rs249957: ERAP1:c.1943+450A>G (chr5-96785338-T-C) – 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.1943+450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 204,674 control chromosomes in the GnomAD database, including 339 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 0.045 ( 212 hom., cov: 32)

Exomes 𝑓: 0.052 ( 127 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

4 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:

ENSG00000248734 (HGNC:):

ENSG00000248734 links:

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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=-0.74).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 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.1943+450A>G	intron	N/A	NP_001035548.1	Q9NZ08-1
ERAP1	NM_001349244.2		c.1943+450A>G	intron	N/A	NP_001336173.1	Q9NZ08-2
ERAP1	NM_016442.5		c.1943+450A>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.1943+450A>G	intron	N/A	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7	TSL:1	c.1943+450A>G	intron	N/A	ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000853356.1		c.1943+450A>G	intron	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6925

AN:

152168

Hom.:

210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0347

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0646

Gnomad OTH

AF:

0.0425

GnomAD4 exome

AF:

0.0523

AC:

2738

AN:

52386

Hom.:

127

Cov.:

AF XY:

0.0571

AC XY:

1568

AN XY:

27454

show subpopulations

African (AFR)

AF:

0.00960

AC:

AN:

1250

American (AMR)

AF:

0.0377

AC:

136

AN:

3608

Ashkenazi Jewish (ASJ)

AF:

0.0833

AC:

AN:

1008

East Asian (EAS)

AF:

0.000323

AC:

AN:

3092

South Asian (SAS)

AF:

0.0873

AC:

647

AN:

7412

European-Finnish (FIN)

AF:

0.0286

AC:

AN:

2206

Middle Eastern (MID)

AF:

0.0976

AC:

AN:

164

European-Non Finnish (NFE)

AF:

0.0533

AC:

1655

AN:

31032

Other (OTH)

AF:

0.0474

AC:

124

AN:

2614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

127

255

382

510

637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.0455

AC:

6928

AN:

152288

Hom.:

212

Cov.:

AF XY:

0.0447

AC XY:

3330

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0131

AC:

544

AN:

41560

American (AMR)

AF:

0.0379

AC:

579

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

371

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5184

South Asian (SAS)

AF:

0.110

AC:

530

AN:

4824

European-Finnish (FIN)

AF:

0.0347

AC:

368

AN:

10620

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0646

AC:

4397

AN:

68016

Other (OTH)

AF:

0.0421

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

324

648

972

1296

1620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0569

Hom.:

Bravo

AF:

0.0423

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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