rs2020869

chr1-171209013-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001460.5(FMO2):c.1476A>G(p.Lys492=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,507,422 control chromosomes in the GnomAD database, including 17,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2032 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15148 hom.)
• Consequence: FMO2 NM_001460.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.564

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-171209013-A-G is Benign according to our data. Variant chr1-171209013-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 769543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.564 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO2	NM_001460.5	c.1476A>G	p.Lys492=	synonymous_variant	9/9	ENST00000209929.10
LOC124900413	XR_007066731.1	n.366-12075T>C		intron_variant, non_coding_transcript_variant
LOC105371611	XR_922278.4	n.514+38568T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMO2	ENST00000209929.10	c.1476A>G	p.Lys492=	synonymous_variant	9/9	1	NM_001460.5	P1
	ENST00000445290.1	n.139-9498T>C		intron_variant, non_coding_transcript_variant		2
	ENST00000669750.1	n.448+38553T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23768 AN: 151998 Hom.: 2026 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.145 AC: 196024 AN: 1355306 Hom.: 15148 Cov.: 19 AF XY: 0.145 AC XY: 98086 AN XY: 675514

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.156 AC: 23785 AN: 152116 Hom.: 2032 Cov.: 32 AF XY: 0.159 AC XY: 11829 AN XY: 74348

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.162

Alfa AF: 0.141 Hom.: 3378

Bravo AF: 0.167

Asia WGS AF: 0.173 AC: 601 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	2.4
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2020869; hg19: chr1-171178152; COSMIC: COSV52947060;