Variant chr1-171196663-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001460.5(FMO2):c.337del(p.Val113Ter) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 402870.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-171196663-TG-T is described in Lovd as [Benign].

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/exons	MANE
FMO2	NM_001460.5 linkuse as main transcript	c.337del	p.Val113Ter	frameshift_variant	4/9	ENST00000209929.10
LOC124900413	XR_007066731.1 linkuse as main transcript	n.640del		non_coding_transcript_exon_variant	2/2
LOC105371611	XR_922278.4 linkuse as main transcript	n.515-28476del		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.337del	p.Val113Ter	frameshift_variant	4/9	1	NM_001460.5	P1
	ENST00000669750.1 linkuse as main transcript	n.449-28476del		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.0567

AC:

14216

AN:

250882

Hom.:

841

AF XY:

0.0537

AC XY:

7281

AN XY:

135580

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 SAS exome

AF:

0.0513

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

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.0871

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0528

Gnomad4 FIN exome

AF:

0.0235

Gnomad4 NFE exome

AF:

0.0460

Gnomad4 OTH exome

AF:

0.0594

GnomAD4 genome

AF:

0.104

AC:

15844

AN:

152198

Hom.:

1493

Cov.:

AF XY:

0.101

AC XY:

7488

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.0567

Gnomad4 ASJ

AF:

0.0940

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0528

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.0463

Gnomad4 OTH

AF:

0.0874

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over