1-171329801-C-T

Variant names:

• chr1-171329801-C-T
• rs714839
• NM_002022.3:c.485-1839C>T

Variant summary

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

The NM_002022.3(FMO4):​c.485-1839C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,046 control chromosomes in the GnomAD database, including 15,247 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 0.44 (15247 hom., cov: 33)
• Consequence: FMO4 NM_002022.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMO4	NM_002022.3	c.485-1839C>T		intron_variant	Intron 5 of 9	ENST00000367749.4	NP_002013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMO4	ENST00000367749.4	c.485-1839C>T		intron_variant	Intron 5 of 9	1	NM_002022.3	ENSP00000356723.3
FMO4	ENST00000462992.1	n.251-1839C>T		intron_variant	Intron 2 of 3	3
FMO4	ENST00000475780.5	n.651+6609C>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67049 AN: 151928 Hom.: 15224 Cov.: 33

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.441 AC: 67111 AN: 152046 Hom.: 15247 Cov.: 33 AF XY: 0.440 AC XY: 32744 AN XY: 74336

African (AFR) AF: 0.545 AC: 22579 AN: 41466

American (AMR) AF: 0.421 AC: 6424 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1525 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1908 AN: 5166

South Asian (SAS) AF: 0.580 AC: 2797 AN: 4822

European-Finnish (FIN) AF: 0.331 AC: 3502 AN: 10570

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27140 AN: 67962

Other (OTH) AF: 0.423 AC: 895 AN: 2114

Alfa AF: 0.411 Hom.: 21495

Bravo AF: 0.448

Asia WGS AF: 0.476 AC: 1654 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.33
PhyloP100		0.092
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: rs714839; hg19: chr1-171298940;