rs7877

chr1-171285751-C-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.*207C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 379,764 control chromosomes in the GnomAD database, including 25,366 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 0.40 (14849 hom., cov: 32)
  • Exomes 𝑓: 0.29 (10517 hom.)
• Consequence: FMO1 NM_001282693.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-171285751-C-T is Benign according to our data. Variant chr1-171285751-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO1	NM_001282693.2	c.*207C>T		3_prime_UTR_variant	9/9	ENST00000617670.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMO1	ENST00000617670.6	c.*207C>T		3_prime_UTR_variant	9/9	1	NM_001282693.2	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60641 AN: 151944 Hom.: 14801 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.378

GnomAD4 exome AF: 0.294 AC: 66850 AN: 227702 Hom.: 10517 Cov.: 3 AF XY: 0.291 AC XY: 33564 AN XY: 115368

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.399 AC: 60739 AN: 152062 Hom.: 14849 Cov.: 32 AF XY: 0.396 AC XY: 29451 AN XY: 74332

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.379

Alfa AF: 0.295 Hom.: 14543

Bravo AF: 0.418

Asia WGS AF: 0.332 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.3
Dann	Benign	0.55

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: rs7877; hg19: chr1-171254890;