1-171209118-CT-CTT

Variant names:

• chr1-171209118-C-CT
• rs2234889
• NM_001460.5:c.1588dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001460.5(FMO2):​c.1588dupT​(p.Cys530LeufsTer30) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 678,584 control chromosomes in the GnomAD database, including 4,860 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1033 hom., cov: 30)
  • Exomes 𝑓: 0.10 (3827 hom.)
• Consequence: FMO2 NM_001460.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47
• Publications: 4 publications found

Genes affected

FMO2 (HGNC:3770): (flavin containing dimethylaniline monoxygenase 2) This gene encodes a flavin-containing monooxygenase family member. It is an NADPH-dependent enzyme that catalyzes the N-oxidation of some primary alkylamines through an N-hydroxylamine intermediate. However, some human populations contain an allele (FMO2*2A) with a premature stop codon, resulting in a protein that is C-terminally-truncated, has no catalytic activity, and is likely degraded rapidly. This gene is found in a cluster with other related family members on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

ENSG00000225243 (HGNC:):

ENSG00000231424 (HGNC:40240):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-171209118-C-CT is Benign according to our data. Variant chr1-171209118-C-CT is described in ClinVar as Benign. ClinVar VariationId is 767726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001460.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO2	NM_001460.5	MANE Select	c.1588dupT	p.Cys530LeufsTer30	frameshift	Exon 9 of 9	NP_001451.2
	FMO2	NM_001365900.2		c.1393dupT	p.Cys465LeufsTer30	frameshift	Exon 8 of 8	NP_001352829.1
	FMO2	NM_001301347.2		c.928dupT	p.Cys310LeufsTer30	frameshift	Exon 7 of 7	NP_001288276.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO2	ENST00000209929.10	TSL:1 MANE Select	c.1588dupT	p.Cys530LeufsTer30	frameshift	Exon 9 of 9	ENSP00000209929.8
	FMO2	ENST00000488431.1	TSL:2	n.580dupT		non_coding_transcript_exon	Exon 2 of 2
	FMO2	ENST00000529935.5	TSL:2	n.*911dupT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000487002.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16345 AN: 151154 Hom.: 1030 Cov.: 30

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.0699

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.104 AC: 54593 AN: 527316 Hom.: 3827 Cov.: 7 AF XY: 0.107 AC XY: 29563 AN XY: 275144

African (AFR) AF: 0.0866 AC: 1177 AN: 13596

American (AMR) AF: 0.186 AC: 3349 AN: 18032

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 1923 AN: 13816

East Asian (EAS) AF: 0.243 AC: 7473 AN: 30770

South Asian (SAS) AF: 0.204 AC: 8636 AN: 42236

European-Finnish (FIN) AF: 0.0746 AC: 2462 AN: 32996

Middle Eastern (MID) AF: 0.133 AC: 278 AN: 2098

European-Non Finnish (NFE) AF: 0.0760 AC: 26246 AN: 345348

Other (OTH) AF: 0.107 AC: 3049 AN: 28424

GnomAD4 genome AF: 0.108 AC: 16375 AN: 151268 Hom.: 1033 Cov.: 30 AF XY: 0.111 AC XY: 8179 AN XY: 73884

African (AFR) AF: 0.0957 AC: 3944 AN: 41204

American (AMR) AF: 0.168 AC: 2540 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3464

East Asian (EAS) AF: 0.244 AC: 1254 AN: 5134

South Asian (SAS) AF: 0.236 AC: 1132 AN: 4800

European-Finnish (FIN) AF: 0.0699 AC: 726 AN: 10384

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0881 AC: 5978 AN: 67822

Other (OTH) AF: 0.108 AC: 227 AN: 2100

Alfa AF: 0.0273 Hom.: 17

Bravo AF: 0.115

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
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: rs2234889; hg19: chr1-171178257; COSMIC: COSV52947052;