Genetic Variant NM_001040458.3:c.2448-38C>T (chr5-96781236-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.2448-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,592,212 control chromosomes in the GnomAD database, including 109,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 11641 hom., cov: 29)

Exomes 𝑓: 0.36 ( 98355 hom. )

Consequence

ERAP1
NM_001040458.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

Publications

25 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=-0.81).

BP6

Variant 5-96781236-G-A is Benign according to our data. Variant chr5-96781236-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688424.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 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.2448-38C>T	intron	N/A	NP_001035548.1	Q9NZ08-1
ERAP1	NM_001349244.2		c.2448-38C>T	intron	N/A	NP_001336173.1	Q9NZ08-2
ERAP1	NM_016442.5		c.2448-38C>T	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.2448-38C>T	intron	N/A	ENSP00000406304.2	Q9NZ08-1
ERAP1	ENST00000296754.7	TSL:1	c.2448-38C>T	intron	N/A	ENSP00000296754.3	Q9NZ08-2
ERAP1	ENST00000853356.1		c.2448-38C>T	intron	N/A	ENSP00000523415.1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58207

AN:

150544

Hom.:

11624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.384

GnomAD2 exomes

AF:

0.358

AC:

89127

AN:

249052

AF XY:

0.369

show subpopulations

Gnomad AFR exome

AF:

0.484

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.365

AC:

525855

AN:

1441550

Hom.:

98355

Cov.:

AF XY:

0.370

AC XY:

265549

AN XY:

718326

show subpopulations

African (AFR)

AF:

0.476

AC:

15690

AN:

32946

American (AMR)

AF:

0.238

AC:

10628

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

11062

AN:

25954

East Asian (EAS)

AF:

0.290

AC:

11471

AN:

39524

South Asian (SAS)

AF:

0.476

AC:

40697

AN:

85490

European-Finnish (FIN)

AF:

0.306

AC:

16298

AN:

53186

Middle Eastern (MID)

AF:

0.427

AC:

2438

AN:

5710

European-Non Finnish (NFE)

AF:

0.361

AC:

395157

AN:

1094548

Other (OTH)

AF:

0.376

AC:

22414

AN:

59620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

14677

29355

44032

58710

73387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12422

24844

37266

49688

62110

<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:

0.387

AC:

58265

AN:

150662

Hom.:

11641

Cov.:

AF XY:

0.384

AC XY:

28240

AN XY:

73480

show subpopulations

African (AFR)

AF:

0.475

AC:

19414

AN:

40844

American (AMR)

AF:

0.299

AC:

4505

AN:

15082

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

1509

AN:

3468

East Asian (EAS)

AF:

0.283

AC:

1445

AN:

5112

South Asian (SAS)

AF:

0.483

AC:

2292

AN:

4748

European-Finnish (FIN)

AF:

0.292

AC:

3017

AN:

10344

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.365

AC:

24718

AN:

67780

Other (OTH)

AF:

0.387

AC:

807

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1757

3515

5272

7030

8787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.374

Hom.:

13310

Bravo

AF:

0.384

Asia WGS

AF:

0.395

AC:

1372

AN:

3476

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

-0.81

CADD

Benign

1.3

(source)

DANN

Benign

0.62

PhyloP100

-1.3

PromoterAI

0.056

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over