chr1-171283148-A-G

Variant names:

• chr1-171283148-A-G
• rs1126692
• NM_001282693.2:c.1188A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001282693.2(FMO1):​c.1188A>G​(p.Val396Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,538,742 control chromosomes in the GnomAD database, including 23,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (6923 hom., cov: 30)
  • Exomes 𝑓: 0.14 (16835 hom.)
• Consequence: FMO1 NM_001282693.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 21 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.87 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 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.1188A>G	p.Val396Val	synonymous	Exon 8 of 9	NP_001269622.1	Q01740-1
	FMO1	NM_001282692.1		c.1200A>G	p.Val400Val	synonymous	Exon 7 of 8	NP_001269621.1	Q01740
	FMO1	NM_002021.3		c.1188A>G	p.Val396Val	synonymous	Exon 8 of 9	NP_002012.1	Q01740-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO1	ENST00000617670.6	TSL:1 MANE Select	c.1188A>G	p.Val396Val	synonymous	Exon 8 of 9	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000354841.4	TSL:1	c.1188A>G	p.Val396Val	synonymous	Exon 7 of 8	ENSP00000346901.4	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.1188A>G	p.Val396Val	synonymous	Exon 8 of 9	ENSP00000356724.3	Q01740-1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36542 AN: 151566 Hom.: 6917 Cov.: 30

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.152 AC: 35794 AN: 235056 AF XY: 0.150

Gnomad AFR exome AF: 0.541

Gnomad AMR exome AF: 0.0792

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.0294

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.139 AC: 192484 AN: 1387060 Hom.: 16835 Cov.: 24 AF XY: 0.140 AC XY: 96881 AN XY: 693472

African (AFR) AF: 0.536 AC: 16323 AN: 30438

American (AMR) AF: 0.0865 AC: 3531 AN: 40836

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3240 AN: 25474

East Asian (EAS) AF: 0.0224 AC: 860 AN: 38432

South Asian (SAS) AF: 0.173 AC: 14124 AN: 81708

European-Finnish (FIN) AF: 0.124 AC: 6618 AN: 53294

Middle Eastern (MID) AF: 0.174 AC: 973 AN: 5608

European-Non Finnish (NFE) AF: 0.131 AC: 138043 AN: 1053630

Other (OTH) AF: 0.152 AC: 8772 AN: 57640

GnomAD4 genome AF: 0.241 AC: 36568 AN: 151682 Hom.: 6923 Cov.: 30 AF XY: 0.237 AC XY: 17548 AN XY: 74138

African (AFR) AF: 0.531 AC: 21903 AN: 41242

American (AMR) AF: 0.124 AC: 1890 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3468

East Asian (EAS) AF: 0.0327 AC: 169 AN: 5166

South Asian (SAS) AF: 0.187 AC: 898 AN: 4808

European-Finnish (FIN) AF: 0.124 AC: 1310 AN: 10534

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9373 AN: 67916

Other (OTH) AF: 0.204 AC: 430 AN: 2110

Alfa AF: 0.161 Hom.: 4624

Bravo AF: 0.251

Asia WGS AF: 0.130 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.59
PhyloP100		-2.9
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: rs1126692; hg19: chr1-171252287;