1-171249227-T-C

Variant names:

• chr1-171249227-T-C
• rs4916192
• NM_001282693.2:c.-7+604T>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.-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
• 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]

FMO1-AS1 (HGNC:40240):

ACMG classification

Our verdict: Benign. The variant received -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.

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.-7+604T>C		intron	N/A	NP_001269622.1	Q01740-1
	FMO1	NM_002021.3		c.-7+613T>C		intron	N/A	NP_002012.1	Q01740-1
	FMO1	NM_001282694.2		c.-7+604T>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.-7+604T>C		intron	N/A	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.-7+613T>C		intron	N/A	ENSP00000356724.3	Q01740-1
	FMO1	ENST00000402921.6	TSL:2	c.-7+604T>C		intron	N/A	ENSP00000385543.2	Q01740-2

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

African (AFR) AF: 0.849 AC: 35207 AN: 41460

American (AMR) AF: 0.632 AC: 9651 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2059 AN: 3466

East Asian (EAS) AF: 0.604 AC: 3110 AN: 5148

South Asian (SAS) AF: 0.616 AC: 2958 AN: 4804

European-Finnish (FIN) AF: 0.381 AC: 4017 AN: 10544

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29391 AN: 67926

Other (OTH) AF: 0.556 AC: 1171 AN: 2106

Alfa AF: 0.495 Hom.: 25492

Bravo AF: 0.613

Asia WGS AF: 0.598 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.81
PhyloP100		-2.1
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: rs4916192; hg19: chr1-171218366;