Genetic Variant NM_001460.5:c.1414C>T (chr1-171208951-C-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.1414C>T(p.Gln472*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,613,588 control chromosomes in the GnomAD database, including 794,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.96 ( 70946 hom., cov: 31)

Exomes 𝑓: 1.0 ( 724053 hom. )

Consequence

FMO2
NM_001460.5 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.91

Publications

23 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:

ENSG00000225243 (HGNC:):

ENSG00000225243 links:

ENSG00000231424 (HGNC:40240):

ENSG00000231424 links:

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ACMG classification

Classification was made for transcript

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

BP6

Variant 1-171208951-C-T is Benign according to our data. Variant chr1-171208951-C-T is described in ClinVar as Benign. ClinVar VariationId is 769222.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMO2	NM_001460.5 link	c.1414C>T	p.Gln472*	stop_gained	Exon 9 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.1414C>T	p.Gln472*	stop_gained	Exon 9 of 9	1	NM_001460.5	ENSP00000209929.8		Q99518

Frequencies

GnomAD3 genomes

AF:

0.964

AC:

146637

AN:

152068

Hom.:

70918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.879

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.989

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.974

GnomAD4 exome

AF:

0.995

AC:

1454424

AN:

1461402

Hom.:

724053

Cov.:

AF XY:

0.995

AC XY:

723575

AN XY:

726990

show subpopulations

African (AFR)

AF:

0.875

AC:

29243

AN:

33436

American (AMR)

AF:

0.992

AC:

44327

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26113

AN:

26114

East Asian (EAS)

AF:

1.00

AC:

39677

AN:

39678

South Asian (SAS)

AF:

0.989

AC:

85234

AN:

86178

European-Finnish (FIN)

AF:

1.00

AC:

53418

AN:

53418

Middle Eastern (MID)

AF:

0.978

AC:

5631

AN:

5760

European-Non Finnish (NFE)

AF:

0.999

AC:

1111050

AN:

1111730

Other (OTH)

AF:

0.989

AC:

59731

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

373

746

1120

1493

1866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21664

43328

64992

86656

108320

<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:

0.964

AC:

146712

AN:

152186

Hom.:

70946

Cov.:

AF XY:

0.965

AC XY:

71793

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.878

AC:

36430

AN:

41498

American (AMR)

AF:

0.985

AC:

15048

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5162

AN:

5162

South Asian (SAS)

AF:

0.989

AC:

4772

AN:

4826

European-Finnish (FIN)

AF:

1.00

AC:

10608

AN:

10608

Middle Eastern (MID)

AF:

0.980

AC:

288

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67959

AN:

68018

Other (OTH)

AF:

0.974

AC:

2061

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

239

478

718

957

1196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.989

Hom.:

339744

Bravo

AF:

0.960

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

PhyloP100

7.9

Vest4

0.56

Splicing

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