rs16864296

Positions:

• chr1-171267187-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282693.2(FMO1):​c.133-356T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 152,280 control chromosomes in the GnomAD database, including 173 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.

• Frequency: Genomes: 𝑓 0.041 (173 hom., cov: 32)
• Consequence: FMO1 NM_001282693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMO1	NM_001282693.2	c.133-356T>C		intron_variant		ENST00000617670.6	NP_001269622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMO1	ENST00000617670.6	c.133-356T>C		intron_variant		1	NM_001282693.2	ENSP00000481732	P1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6310 AN: 152162 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.0502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0414 AC: 6307 AN: 152280 Hom.: 173 Cov.: 32 AF XY: 0.0415 AC XY: 3092 AN XY: 74454

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0394

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0678

Gnomad4 SAS AF: 0.0158

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0580

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0509 Hom.: 280

Bravo AF: 0.0396

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.62

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: rs16864296; hg19: chr1-171236326;