rs2076320

Variant names:

• chr1-171275620-A-C
• rs2076320
• NM_001282693.2:c.484+112A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-171275620-A-C
• chr1-171275620-A-T

Variant summary

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

The NM_001282693.2(FMO1):​c.484+112A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 713,908 control chromosomes in the GnomAD database, including 8,109 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 0.14 (1552 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6557 hom.)
• Consequence: FMO1 NM_001282693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 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.484+112A>C		intron	N/A	NP_001269622.1	Q01740-1
	FMO1	NM_001282692.1		c.496+112A>C		intron	N/A	NP_001269621.1	Q01740
	FMO1	NM_002021.3		c.484+112A>C		intron	N/A	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.484+112A>C		intron	N/A	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000354841.4	TSL:1	c.484+112A>C		intron	N/A	ENSP00000346901.4	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.484+112A>C		intron	N/A	ENSP00000356724.3	Q01740-1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20803 AN: 151828 Hom.: 1547 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.148 AC: 83392 AN: 561962 Hom.: 6557 AF XY: 0.147 AC XY: 42561 AN XY: 289268

African (AFR) AF: 0.0971 AC: 1306 AN: 13444

American (AMR) AF: 0.293 AC: 5275 AN: 17992

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 1950 AN: 13030

East Asian (EAS) AF: 0.249 AC: 7370 AN: 29614

South Asian (SAS) AF: 0.140 AC: 4376 AN: 31332

European-Finnish (FIN) AF: 0.134 AC: 4908 AN: 36566

Middle Eastern (MID) AF: 0.123 AC: 317 AN: 2586

European-Non Finnish (NFE) AF: 0.138 AC: 53749 AN: 388726

Other (OTH) AF: 0.144 AC: 4141 AN: 28672

GnomAD4 genome AF: 0.137 AC: 20845 AN: 151946 Hom.: 1552 Cov.: 32 AF XY: 0.139 AC XY: 10316 AN XY: 74274

African (AFR) AF: 0.0983 AC: 4075 AN: 41436

American (AMR) AF: 0.223 AC: 3407 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1045 AN: 5166

South Asian (SAS) AF: 0.152 AC: 729 AN: 4798

European-Finnish (FIN) AF: 0.136 AC: 1443 AN: 10578

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9210 AN: 67926

Other (OTH) AF: 0.151 AC: 320 AN: 2116

Alfa AF: 0.138 Hom.: 5080

Bravo AF: 0.144

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.80
PhyloP100		1.8
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: rs2076320; hg19: chr1-171244759;