ENST00000354841:c.-11T>C

Variant names:

• chr1-171258077-T-C
• rs10912675
• ENST00000354841.4:c.-11T>C

Variant summary

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

The ENST00000354841.4(FMO1):​c.-11T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,613,342 control chromosomes in the GnomAD database, including 77,661 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 (14559 hom., cov: 32)
  • Exomes 𝑓: 0.28 (63102 hom.)
• Consequence: FMO1 ENST00000354841.4 5_prime_UTR
• Scores: Splicing: ADA: 0.0001335
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 19 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354841.4. 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.-6-5T>C		splice_region intron	N/A	NP_001269622.1	Q01740-1
	FMO1	NM_001282692.1		c.2T>C	p.Met1?	start_lost	Exon 1 of 8	NP_001269621.1	Q01740
	FMO1	NM_002021.3		c.-6-5T>C		splice_region intron	N/A	NP_002012.1	Q01740-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO1	ENST00000354841.4	TSL:1	c.-11T>C		5_prime_UTR	Exon 1 of 8	ENSP00000346901.4	Q01740-1
	FMO1	ENST00000617670.6	TSL:1 MANE Select	c.-6-5T>C		splice_region intron	N/A	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.-6-5T>C		splice_region intron	N/A	ENSP00000356724.3	Q01740-1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59893 AN: 151948 Hom.: 14510 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.370

GnomAD2 exomes AF: 0.310 AC: 77738 AN: 251118 AF XY: 0.306

Gnomad AFR exome AF: 0.711

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.190

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.281

GnomAD4 exome AF: 0.284 AC: 414494 AN: 1461276 Hom.: 63102 Cov.: 33 AF XY: 0.284 AC XY: 206651 AN XY: 726936

African (AFR) AF: 0.714 AC: 23912 AN: 33468

American (AMR) AF: 0.307 AC: 13706 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7458 AN: 26132

East Asian (EAS) AF: 0.206 AC: 8188 AN: 39682

South Asian (SAS) AF: 0.336 AC: 28968 AN: 86242

European-Finnish (FIN) AF: 0.273 AC: 14572 AN: 53364

Middle Eastern (MID) AF: 0.297 AC: 1702 AN: 5738

European-Non Finnish (NFE) AF: 0.268 AC: 297934 AN: 1111570

Other (OTH) AF: 0.299 AC: 18054 AN: 60370

GnomAD4 genome AF: 0.395 AC: 59993 AN: 152066 Hom.: 14559 Cov.: 32 AF XY: 0.391 AC XY: 29100 AN XY: 74336

African (AFR) AF: 0.698 AC: 28963 AN: 41470

American (AMR) AF: 0.311 AC: 4755 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3466

East Asian (EAS) AF: 0.201 AC: 1036 AN: 5144

South Asian (SAS) AF: 0.351 AC: 1693 AN: 4818

European-Finnish (FIN) AF: 0.278 AC: 2936 AN: 10580

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18582 AN: 67990

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.326 Hom.: 19358

Bravo AF: 0.408

Asia WGS AF: 0.309 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.65
DANN	Benign	0.51
PhyloP100		-1.4
PromoterAI		0.11	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.010		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: rs10912675; hg19: chr1-171227216; COSMIC: COSV61448222; COSMIC: COSV61448222;