dbSNP rs1037475: METAP1:c.166+2641A>G (chr4-99031559-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000296411.11(METAP1):c.166+2641A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,286,878 control chromosomes in the GnomAD database, including 203,240 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 0.47 ( 18543 hom., cov: 32)

Exomes 𝑓: 0.57 ( 184697 hom. )

Consequence

METAP1
ENST00000296411.11 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0710

Publications

17 publications found

Variant links:

Genes affected

METAP1 (HGNC:15789): (methionyl aminopeptidase 1) Predicted to enable aminopeptidase activity and metalloexopeptidase activity. Involved in platelet aggregation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

METAP1 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=-0.91).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000296411.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METAP1	NM_015143.3	MANE Select	c.166+2641A>G		intron	N/A	NP_055958.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
METAP1	ENST00000296411.11	TSL:1 MANE Select	c.166+2641A>G	intron	N/A	ENSP00000296411.6
METAP1	ENST00000510107.5	TSL:5	n.*26A>G	non_coding_transcript_exon	Exon 3 of 8	ENSP00000427187.1
METAP1	ENST00000510107.5	TSL:5	n.*26A>G	3_prime_UTR	Exon 3 of 8	ENSP00000427187.1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72135

AN:

151966

Hom.:

18546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.671

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.504

GnomAD2 exomes

AF:

0.516

AC:

66198

AN:

128330

AF XY:

0.537

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.593

Gnomad EAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.569

Gnomad NFE exome

AF:

0.567

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.565

AC:

641549

AN:

1134794

Hom.:

184697

Cov.:

AF XY:

0.571

AC XY:

317957

AN XY:

556808

show subpopulations

African (AFR)

AF:

0.293

AC:

7137

AN:

24374

American (AMR)

AF:

0.404

AC:

11411

AN:

28266

Ashkenazi Jewish (ASJ)

AF:

0.592

AC:

9426

AN:

15928

East Asian (EAS)

AF:

0.186

AC:

2382

AN:

12836

South Asian (SAS)

AF:

0.691

AC:

52620

AN:

76140

European-Finnish (FIN)

AF:

0.555

AC:

7015

AN:

12638

Middle Eastern (MID)

AF:

0.624

AC:

2745

AN:

4402

European-Non Finnish (NFE)

AF:

0.572

AC:

525940

AN:

918762

Other (OTH)

AF:

0.552

AC:

22873

AN:

41448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

13010

26020

39031

52041

65051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16858

33716

50574

67432

84290

<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:

0.474

AC:

72158

AN:

152084

Hom.:

18543

Cov.:

AF XY:

0.477

AC XY:

35454

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.305

AC:

12646

AN:

41486

American (AMR)

AF:

0.459

AC:

7007

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2047

AN:

3472

East Asian (EAS)

AF:

0.192

AC:

994

AN:

5174

South Asian (SAS)

AF:

0.672

AC:

3241

AN:

4822

European-Finnish (FIN)

AF:

0.546

AC:

5769

AN:

10570

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38658

AN:

67980

Other (OTH)

AF:

0.504

AC:

1065

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1804

3607

5411

7214

9018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.532

Hom.:

77109

Bravo

AF:

0.452

Asia WGS

AF:

0.445

AC:

1545

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.56

PhyloP100

-0.071

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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