Variant chr1-171185820-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001460.5(FMO2):c.107A>G(p.Asp36Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 1,613,426 control chromosomes in the GnomAD database, including 5,132 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.073 ( 452 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4680 hom. )

Consequence

FMO2
NM_001460.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.29

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027392507).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO2	NM_001460.5 linkuse as main transcript	c.107A>G	p.Asp36Gly	missense_variant	2/9	ENST00000209929.10
LOC105371611	XR_922278.4 linkuse as main transcript	n.515-17632T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMO2	ENST00000209929.10 linkuse as main transcript	c.107A>G	p.Asp36Gly	missense_variant	2/9	1	NM_001460.5	P1
	ENST00000669750.1 linkuse as main transcript	n.449-17632T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0726

AC:

11042

AN:

152072

Hom.:

452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0713

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0673

Gnomad OTH

AF:

0.0716

GnomAD3 exomes

AF:

0.0795

AC:

19983

AN:

251384

Hom.:

1012

AF XY:

0.0832

AC XY:

11298

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.0457

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.135

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.0485

Gnomad NFE exome

AF:

0.0700

Gnomad OTH exome

AF:

0.0882

GnomAD4 exome

AF:

0.0747

AC:

109211

AN:

1461236

Hom.:

4680

Cov.:

AF XY:

0.0768

AC XY:

55794

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.0693

Gnomad4 AMR exome

AF:

0.0470

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.0515

Gnomad4 NFE exome

AF:

0.0689

Gnomad4 OTH exome

AF:

0.0855

GnomAD4 genome

AF:

0.0726

AC:

11044

AN:

152190

Hom.:

452

Cov.:

AF XY:

0.0729

AC XY:

5423

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0713

Gnomad4 AMR

AF:

0.0623

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0477

Gnomad4 NFE

AF:

0.0673

Gnomad4 OTH

AF:

0.0718

Alfa

AF:

0.0747

Hom.:

1108

Bravo

AF:

0.0720

TwinsUK

AF:

0.0715

AC:

265

ALSPAC

AF:

0.0643

AC:

248

ESP6500AA

AF:

0.0658

AC:

290

ESP6500EA

AF:

0.0678

AC:

583

ExAC

AF:

0.0815

AC:

9890

Asia WGS

AF:

0.117

AC:

405

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.45

MutationTaster

Benign

0.0000047

P;P

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.8

D;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.012

D;.

Sift4G

Uncertain

0.017

D;T

Vest4

0.25

ClinPred

0.044

GERP RS

5.7

gMVP

0.75

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

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