Genetic Variant NM_001040458.3:c.798+83C>T (chr5-96797092-G-A) – 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.798+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,553,910 control chromosomes in the GnomAD database, including 13,798 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 0.12 ( 1189 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12609 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.328

Publications

9 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP1	NM_001040458.3 link	c.798+83C>T		intron_variant	Intron 4 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.798+83C>T	intron_variant	Intron 4 of 18	1	NM_001040458.3	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7 link	c.798+83C>T	intron_variant	Intron 4 of 19	1		ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000503921.5 link	c.*155C>T	downstream_gene_variant		4		ENSP00000427025.1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17903

AN:

151910

Hom.:

1185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0809

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.111

GnomAD4 exome

AF:

0.132

AC:

184411

AN:

1401882

Hom.:

12609

AF XY:

0.131

AC XY:

91490

AN XY:

700202

show subpopulations

African (AFR)

AF:

0.0795

AC:

2570

AN:

32322

American (AMR)

AF:

0.176

AC:

7666

AN:

43630

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

3468

AN:

25686

East Asian (EAS)

AF:

0.181

AC:

7108

AN:

39176

South Asian (SAS)

AF:

0.109

AC:

9149

AN:

84314

European-Finnish (FIN)

AF:

0.171

AC:

8937

AN:

52288

Middle Eastern (MID)

AF:

0.190

AC:

1080

AN:

5672

European-Non Finnish (NFE)

AF:

0.129

AC:

137125

AN:

1060410

Other (OTH)

AF:

0.125

AC:

7308

AN:

58384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

8058

16117

24175

32234

40292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4986

9972

14958

19944

24930

<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:

0.118

AC:

17910

AN:

152028

Hom.:

1189

Cov.:

AF XY:

0.118

AC XY:

8799

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0808

AC:

3351

AN:

41472

American (AMR)

AF:

0.122

AC:

1858

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

458

AN:

3472

East Asian (EAS)

AF:

0.166

AC:

855

AN:

5166

South Asian (SAS)

AF:

0.107

AC:

517

AN:

4818

European-Finnish (FIN)

AF:

0.171

AC:

1797

AN:

10538

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8714

AN:

67970

Other (OTH)

AF:

0.110

AC:

233

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

788

1576

2364

3152

3940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<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:

0.123

Hom.:

1584

Bravo

AF:

0.115

Asia WGS

AF:

0.144

AC:

500

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.5

(source)

DANN

Benign

0.56

PhyloP100

0.33

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

Computational scores

Splicing

Publications

Other links and lift over