rs742350

Positions:

• chr1-171280905-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001282693.2(FMO1):​c.747C>T​(p.Thr249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,384 control chromosomes in the GnomAD database, including 22,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (5385 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17191 hom.)
• Consequence: FMO1 NM_001282693.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

Genes affected

FMO1 (HGNC:3769): (flavin containing dimethylaniline monoxygenase 1) Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-171280905-C-T is Benign according to our data. Variant chr1-171280905-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO1	NM_001282693.2	c.747C>T	p.Thr249=	synonymous_variant	6/9	ENST00000617670.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMO1	ENST00000617670.6	c.747C>T	p.Thr249=	synonymous_variant	6/9	1	NM_001282693.2	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33327 AN: 151964 Hom.: 5383 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.191

GnomAD3 exomes AF: 0.146 AC: 36603 AN: 251304 Hom.: 3881 AF XY: 0.145 AC XY: 19682 AN XY: 135820

Gnomad AFR exome AF: 0.465

Gnomad AMR exome AF: 0.0762

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.0206

Gnomad SAS exome AF: 0.179

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.141 AC: 206730 AN: 1461302 Hom.: 17191 Cov.: 32 AF XY: 0.142 AC XY: 103265 AN XY: 726976

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.0821

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0182

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.219 AC: 33340 AN: 152082 Hom.: 5385 Cov.: 32 AF XY: 0.215 AC XY: 15981 AN XY: 74368

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.190

Alfa AF: 0.153 Hom.: 4980

Bravo AF: 0.226

Asia WGS AF: 0.131 AC: 456 AN: 3478

EpiCase AF: 0.136

EpiControl AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.3
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs742350; hg19: chr1-171250044; COSMIC: COSV61445056; COSMIC: COSV61445056;