1-171254812-G-C

Variant names:

• chr1-171254812-G-C
• rs4433435
• NM_001282693.2:c.-6-3270G>C

Variant summary

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

The NM_001282693.2(FMO1):​c.-6-3270G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,008 control chromosomes in the GnomAD database, including 20,794 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 0.50 (20794 hom., cov: 32)
• Consequence: FMO1 NM_001282693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMO1	NM_001282693.2	c.-6-3270G>C		intron_variant	Intron 1 of 8	ENST00000617670.6	NP_001269622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMO1	ENST00000617670.6	c.-6-3270G>C		intron_variant	Intron 1 of 8	1	NM_001282693.2	ENSP00000481732.1
FMO1	ENST00000367750.7	c.-6-3270G>C		intron_variant	Intron 1 of 8	1		ENSP00000356724.3
FMO1	ENST00000402921.6	c.-6-3270G>C		intron_variant	Intron 1 of 7	2		ENSP00000385543.2

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75625 AN: 151890 Hom.: 20757 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.498 AC: 75719 AN: 152008 Hom.: 20794 Cov.: 32 AF XY: 0.499 AC XY: 37077 AN XY: 74266

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.458

Alfa AF: 0.294 Hom.: 838

Bravo AF: 0.510

Asia WGS AF: 0.472 AC: 1643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.46

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: rs4433435; hg19: chr1-171223951;