Variant chr1-171203982-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001460.5(FMO2):c.745C>T(p.Arg249Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000969 in 1,613,638 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0044 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 5 hom. )

Consequence

FMO2
NM_001460.5 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0120

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FMO2	NM_001460.5 linkuse as main transcript	c.745C>T	p.Arg249Ter	stop_gained	6/9	ENST00000209929.10
LOC124900413	XR_007066731.1 linkuse as main transcript	n.366-7044G>A		intron_variant, non_coding_transcript_variant
LOC105371611	XR_922278.4 linkuse as main transcript	n.515-35794G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FMO2	ENST00000209929.10 linkuse as main transcript	c.745C>T	p.Arg249Ter	stop_gained	6/9	1	NM_001460.5	P1
	ENST00000445290.1 linkuse as main transcript	n.139-4467G>A		intron_variant, non_coding_transcript_variant		2
	ENST00000669750.1 linkuse as main transcript	n.449-35794G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00125

AC:

314

AN:

250824

Hom.:

AF XY:

0.000989

AC XY:

134

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000613

AC:

896

AN:

1461436

Hom.:

Cov.:

AF XY:

0.000541

AC XY:

393

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.000873

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00438

AC:

667

AN:

152202

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

322

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.00494

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00157

AC:

191

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.43

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.067

MutationTaster

Benign

1.0

A;A

Vest4

0.84

GERP RS

4.2

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over