NM_001282693.2:c.485-10T>C

Variant names:

• chr1-171278719-T-C
• rs28360407
• NM_001282693.2:c.485-10T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001282693.2(FMO1):​c.485-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,556,348 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (12 hom.)
• Consequence: FMO1 NM_001282693.2 intron
• Scores: Splicing: ADA: 0.001418
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.11
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-171278719-T-C is Benign according to our data. Variant chr1-171278719-T-C is described in ClinVar as Benign. ClinVar VariationId is 782396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00622 (947/152346) while in subpopulation AFR AF = 0.0203 (843/41586). AF 95% confidence interval is 0.0191. There are 12 homozygotes in GnomAd4. There are 439 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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.485-10T>C		intron	N/A	NP_001269622.1	Q01740-1
	FMO1	NM_001282692.1		c.497-10T>C		intron	N/A	NP_001269621.1	Q01740
	FMO1	NM_002021.3		c.485-10T>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.485-10T>C		intron	N/A	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000354841.4	TSL:1	c.485-10T>C		intron	N/A	ENSP00000346901.4	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.485-10T>C		intron	N/A	ENSP00000356724.3	Q01740-1

Frequencies

GnomAD3 genomes AF: 0.00621 AC: 946 AN: 152228 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00186 AC: 434 AN: 232840 AF XY: 0.00127

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.00233

Gnomad ASJ exome AF: 0.00142

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000129

Gnomad OTH exome AF: 0.00146

GnomAD4 exome AF: 0.000707 AC: 992 AN: 1404002 Hom.: 12 Cov.: 26 AF XY: 0.000578 AC XY: 403 AN XY: 696674

African (AFR) AF: 0.0205 AC: 650 AN: 31772

American (AMR) AF: 0.00253 AC: 102 AN: 40308

Ashkenazi Jewish (ASJ) AF: 0.00164 AC: 40 AN: 24452

East Asian (EAS) AF: 0.00 AC: 0 AN: 38816

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52028

Middle Eastern (MID) AF: 0.00198 AC: 11 AN: 5546

European-Non Finnish (NFE) AF: 0.0000716 AC: 77 AN: 1075234

Other (OTH) AF: 0.00193 AC: 111 AN: 57590

GnomAD4 genome AF: 0.00622 AC: 947 AN: 152346 Hom.: 12 Cov.: 32 AF XY: 0.00589 AC XY: 439 AN XY: 74496

African (AFR) AF: 0.0203 AC: 843 AN: 41586

American (AMR) AF: 0.00458 AC: 70 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68030

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00401 Hom.: 2

Bravo AF: 0.00766

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.7
DANN	Benign	0.70
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0014
dbscSNV1_RF	Benign	0.022
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: rs28360407; hg19: chr1-171247858;