rs16864387

chr1-171314704-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002022.3(FMO4):c.-151+291T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,018 control chromosomes in the GnomAD database, including 4,321 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 0.20 (4321 hom., cov: 32)
• Consequence: FMO4 NM_002022.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

FMO4 (HGNC:3772): (flavin containing dimethylaniline monoxygenase 4) Metabolic N-oxidation of diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man. This results in a small subpopulation with reduced TMA N-oxidation capacity and causes fish odor syndrome (Trimethylaminuria). Three forms of the enzyme 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. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO4	NM_002022.3	c.-151+291T>C		intron_variant		ENST00000367749.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMO4	ENST00000367749.4	c.-151+291T>C		intron_variant		1	NM_002022.3	P1
FMO4	ENST00000475780.5	n.180+291T>C		intron_variant, non_coding_transcript_variant		2
FMO4	ENST00000497228.5	n.206+291T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30880 AN: 151900 Hom.: 4321 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0224

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.203 AC: 30893 AN: 152018 Hom.: 4321 Cov.: 32 AF XY: 0.199 AC XY: 14819 AN XY: 74310

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0222

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.173

Alfa AF: 0.156 Hom.: 981

Bravo AF: 0.207

Asia WGS AF: 0.122 AC: 425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.86
Dann	Benign	0.60

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: rs16864387; hg19: chr1-171283843;