1-171254812-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282693.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO1	NM_001282693.2	MANE Select	c.-6-3270G>C		intron	N/A	NP_001269622.1	Q01740-1
	FMO1	NM_002021.3		c.-6-3270G>C		intron	N/A	NP_002012.1	Q01740-1
	FMO1	NM_001282694.2		c.-6-3270G>C		intron	N/A	NP_001269623.1	Q01740-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO1	ENST00000617670.6	TSL:1 MANE Select	c.-6-3270G>C		intron	N/A	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.-6-3270G>C		intron	N/A	ENSP00000356724.3	Q01740-1
	FMO1	ENST00000402921.6	TSL:2	c.-6-3270G>C		intron	N/A	ENSP00000385543.2	Q01740-2

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

African (AFR) AF: 0.752 AC: 31174 AN: 41480

American (AMR) AF: 0.446 AC: 6809 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1429 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1837 AN: 5166

South Asian (SAS) AF: 0.538 AC: 2591 AN: 4816

European-Finnish (FIN) AF: 0.402 AC: 4230 AN: 10532

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26188 AN: 67954

Other (OTH) AF: 0.458 AC: 966 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4433435; hg19: chr1-171223951;