dbSNP rs28369860: FMO2:p.Val113fs (chr1-171196663-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001460.5(FMO2):c.337delG(p.Val113fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,612,710 control chromosomes in the GnomAD database, including 4,390 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.10 ( 1493 hom., cov: 31)

Exomes 𝑓: 0.051 ( 2897 hom. )

Consequence

FMO2
NM_001460.5 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.92

Publications

16 publications found

Variant links:

Genes affected

FMO2 (HGNC:3770): (flavin containing dimethylaniline monoxygenase 2) This gene encodes a flavin-containing monooxygenase family member. It is an NADPH-dependent enzyme that catalyzes the N-oxidation of some primary alkylamines through an N-hydroxylamine intermediate. However, some human populations contain an allele (FMO2*2A) with a premature stop codon, resulting in a protein that is C-terminally-truncated, has no catalytic activity, and is likely degraded rapidly. This gene is found in a cluster with other related family members on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

FMO2 links:

LOC124900413 (HGNC:):

LOC124900413 links:

ENSG00000231424 (HGNC:40240):

ENSG00000231424 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-171196663-TG-T is Benign according to our data. Variant chr1-171196663-TG-T is described in ClinVar as Benign. ClinVar VariationId is 402870.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMO2	NM_001460.5 link	c.337delG	p.Val113fs	frameshift_variant	Exon 4 of 9	ENST00000209929.10	NP_001451.2	Q99518Q5JPC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMO2	ENST00000209929.10 link	c.337delG	p.Val113fs	frameshift_variant	Exon 4 of 9	1	NM_001460.5	ENSP00000209929.8		Q99518

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15819

AN:

152080

Hom.:

1490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0568

Gnomad ASJ

AF:

0.0940

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0463

Gnomad OTH

AF:

0.0883

GnomAD2 exomes

AF:

0.0567

AC:

14216

AN:

250882

AF XY:

0.0537

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.0361

Gnomad ASJ exome

AF:

0.0896

Gnomad EAS exome

AF:

0.000545

Gnomad FIN exome

AF:

0.0238

Gnomad NFE exome

AF:

0.0467

Gnomad OTH exome

AF:

0.0518

GnomAD4 exome

AF:

0.0506

AC:

73873

AN:

1460512

Hom.:

2897

Cov.:

AF XY:

0.0499

AC XY:

36268

AN XY:

726604

show subpopulations

African (AFR)

AF:

0.269

AC:

8979

AN:

33434

American (AMR)

AF:

0.0389

AC:

1738

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0871

AC:

2275

AN:

26132

East Asian (EAS)

AF:

0.000202

AC:

AN:

39686

South Asian (SAS)

AF:

0.0528

AC:

4549

AN:

86190

European-Finnish (FIN)

AF:

0.0235

AC:

1253

AN:

53402

Middle Eastern (MID)

AF:

0.0782

AC:

402

AN:

5140

European-Non Finnish (NFE)

AF:

0.0460

AC:

51088

AN:

1111570

Other (OTH)

AF:

0.0594

AC:

3581

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

3006

6011

9017

12022

15028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2062

4124

6186

8248

10310

<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:

0.104

AC:

15844

AN:

152198

Hom.:

1493

Cov.:

AF XY:

0.101

AC XY:

7488

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.260

AC:

10794

AN:

41472

American (AMR)

AF:

0.0567

AC:

868

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0940

AC:

326

AN:

3468

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.0528

AC:

255

AN:

4826

European-Finnish (FIN)

AF:

0.0232

AC:

246

AN:

10612

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0463

AC:

3148

AN:

68020

Other (OTH)

AF:

0.0874

AC:

185

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

662

1324

1986

2648

3310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0354

Hom.:

Bravo

AF:

0.114

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 1453/12520=11.6% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Mutation Taster

=147/53

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over