rs141653324

Variant names:

• chr1-171205323-G-A
• rs141653324
• NM_001460.5:c.872G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-171205323-G-A
• chr1-171205323-G-C
• chr1-171205323-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001460.5(FMO2):​c.872G>A​(p.Arg291His) variant causes a missense change. The variant allele was found at a frequency of 0.000653 in 1,613,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R291P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (0 hom.)
• Consequence: FMO2 NM_001460.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86
• Publications: 3 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:):

FMO1-AS1 (HGNC:40240):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059536994).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO2	NM_001460.5	MANE Select	c.872G>A	p.Arg291His	missense	Exon 7 of 9	NP_001451.2	Q99518
	FMO2	NM_001365900.2		c.677G>A	p.Arg226His	missense	Exon 6 of 8	NP_001352829.1
	FMO2	NM_001301347.2		c.212G>A	p.Arg71His	missense	Exon 5 of 7	NP_001288276.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO2	ENST00000209929.10	TSL:1 MANE Select	c.872G>A	p.Arg291His	missense	Exon 7 of 9	ENSP00000209929.8	Q99518
	FMO2	ENST00000895514.1		c.872G>A	p.Arg291His	missense	Exon 7 of 9	ENSP00000565573.1
	FMO2	ENST00000895513.1		c.869G>A	p.Arg290His	missense	Exon 7 of 9	ENSP00000565572.1

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 67 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000447 AC: 112 AN: 250636 AF XY: 0.000458

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000813

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000675 AC: 986 AN: 1461224 Hom.: 0 Cov.: 31 AF XY: 0.000662 AC XY: 481 AN XY: 726912

African (AFR) AF: 0.000239 AC: 8 AN: 33454

American (AMR) AF: 0.000269 AC: 12 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86232

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53390

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5760

European-Non Finnish (NFE) AF: 0.000828 AC: 920 AN: 1111556

Other (OTH) AF: 0.000364 AC: 22 AN: 60358

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74412

African (AFR) AF: 0.000265 AC: 11 AN: 41538

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10598

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

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000778 Hom.: 0

Bravo AF: 0.000393

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000494 AC: 60

EpiCase AF: 0.000601

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	0.13
Eigen_PC	Benign	0.068
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.93	T
PhyloP100		4.9
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.26
Sift	Benign	0.36	T
Sift4G	Benign	0.45	T
Vest4		0.15
MVP		0.71
ClinPred		0.052	T
GERP RS		2.6
gMVP		0.50
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141653324; hg19: chr1-171174462; COSMIC: COSV52946698; COSMIC: COSV52946698;