1-171267084-A-G

Variant names:

• chr1-171267084-A-G
• rs10912694
• NM_001282693.2:c.133-459A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282693.2(FMO1):​c.133-459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,092 control chromosomes in the GnomAD database, including 14,376 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 0.39 (14376 hom., cov: 33)
• Consequence: FMO1 NM_001282693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 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.133-459A>G		intron	N/A	NP_001269622.1	Q01740-1
	FMO1	NM_001282692.1		c.145-459A>G		intron	N/A	NP_001269621.1	Q01740
	FMO1	NM_002021.3		c.133-459A>G		intron	N/A	NP_002012.1	Q01740-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO1	ENST00000617670.6	TSL:1 MANE Select	c.133-459A>G		intron	N/A	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000354841.4	TSL:1	c.133-459A>G		intron	N/A	ENSP00000346901.4	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.133-459A>G		intron	N/A	ENSP00000356724.3	Q01740-1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59304 AN: 151974 Hom.: 14331 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.391 AC: 59399 AN: 152092 Hom.: 14376 Cov.: 33 AF XY: 0.387 AC XY: 28737 AN XY: 74348

African (AFR) AF: 0.697 AC: 28910 AN: 41478

American (AMR) AF: 0.311 AC: 4751 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1015 AN: 5162

South Asian (SAS) AF: 0.333 AC: 1604 AN: 4816

European-Finnish (FIN) AF: 0.261 AC: 2761 AN: 10590

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18352 AN: 67974

Other (OTH) AF: 0.369 AC: 779 AN: 2112

Alfa AF: 0.309 Hom.: 11388

Bravo AF: 0.406

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.35
PhyloP100		-1.2
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: rs10912694; hg19: chr1-171236223;