rs2076320

Positions:

• chr1-171275620-A-C
• chr1-171275620-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001282693.2(FMO1):​c.484+112A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 713,908 control chromosomes in the GnomAD database, including 8,109 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 0.14 (1552 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6557 hom.)
• Consequence: FMO1 NM_001282693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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]

FMO1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-171275620-A-C is Benign according to our data. Variant chr1-171275620-A-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMO1	NM_001282693.2	c.484+112A>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.484+112A>C		intron_variant		1	NM_001282693.2	ENSP00000481732.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20803 AN: 151828 Hom.: 1547 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.148 AC: 83392 AN: 561962 Hom.: 6557 AF XY: 0.147 AC XY: 42561 AN XY: 289268

Gnomad4 AFR exome AF: 0.0971

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.137 AC: 20845 AN: 151946 Hom.: 1552 Cov.: 32 AF XY: 0.139 AC XY: 10316 AN XY: 74274

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.151

Alfa AF: 0.137 Hom.: 3206

Bravo AF: 0.144

Asia WGS AF: 0.185 AC: 644 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	9.2
DANN	Benign	0.80

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: rs2076320; hg19: chr1-171244759;