Genetic Variant NM_001282693.2:c.*207C>T (chr1-171285751-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001282693.2(FMO1):c.*207C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 379,764 control chromosomes in the GnomAD database, including 25,366 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 0.40 ( 14849 hom., cov: 32)

Exomes 𝑓: 0.29 ( 10517 hom. )

Consequence

FMO1
NM_001282693.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.116

Publications

25 publications found

Variant links:

Genes affected

FMO1 (HGNC:3769): (flavin containing dimethylaniline monoxygenase 1) Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

FMO1 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMO1	NM_001282693.2 link	c.*207C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000617670.6	NP_001269622.1	Q01740-1A0A024R934B2RCG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMO1	ENST00000617670.6 link	c.*207C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_001282693.2	ENSP00000481732.1		Q01740-1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60641

AN:

151944

Hom.:

14801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.294

AC:

66850

AN:

227702

Hom.:

10517

Cov.:

AF XY:

0.291

AC XY:

33564

AN XY:

115368

show subpopulations

African (AFR)

AF:

0.687

AC:

4640

AN:

6754

American (AMR)

AF:

0.399

AC:

2804

AN:

7030

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

2324

AN:

8684

East Asian (EAS)

AF:

0.284

AC:

5975

AN:

21074

South Asian (SAS)

AF:

0.329

AC:

914

AN:

2774

European-Finnish (FIN)

AF:

0.258

AC:

4542

AN:

17588

Middle Eastern (MID)

AF:

0.277

AC:

329

AN:

1188

European-Non Finnish (NFE)

AF:

0.275

AC:

40481

AN:

147374

Other (OTH)

AF:

0.318

AC:

4841

AN:

15236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2098

4196

6294

8392

10490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<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:

0.399

AC:

60739

AN:

152062

Hom.:

14849

Cov.:

AF XY:

0.396

AC XY:

29451

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.701

AC:

29068

AN:

41486

American (AMR)

AF:

0.359

AC:

5486

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

970

AN:

3468

East Asian (EAS)

AF:

0.235

AC:

1211

AN:

5156

South Asian (SAS)

AF:

0.340

AC:

1641

AN:

4826

European-Finnish (FIN)

AF:

0.261

AC:

2759

AN:

10570

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.273

AC:

18591

AN:

67976

Other (OTH)

AF:

0.379

AC:

800

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1638

3277

4915

6554

8192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.314

Hom.:

37340

Bravo

AF:

0.418

Asia WGS

AF:

0.332

AC:

1155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.55

PhyloP100

-0.12

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