1-171249227-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.-7+604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,938 control chromosomes in the GnomAD database, including 28,105 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 0.58 (28105 hom., cov: 31)
• Consequence: FMO1 NM_001282693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO1	NM_001282693.2	c.-7+604T>C		intron_variant		ENST00000617670.6
LOC105371611	XR_922278.4	n.368-1500A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMO1	ENST00000617670.6	c.-7+604T>C		intron_variant		1	NM_001282693.2	P1
	ENST00000669750.1	n.287-1500A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87956 AN: 151820 Hom.: 28049 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.580 AC: 88072 AN: 151938 Hom.: 28105 Cov.: 31 AF XY: 0.579 AC XY: 43042 AN XY: 74278

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.556

Alfa AF: 0.474 Hom.: 17756

Bravo AF: 0.613

Asia WGS AF: 0.598 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.14
Dann	Benign	0.81

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: rs4916192; hg19: chr1-171218366;