rs6661174

chr1-171208951-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_001460.5(FMO2):c.1414C>T(p.Gln472Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,613,588 control chromosomes in the GnomAD database, including 794,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (70946 hom., cov: 31)
  • Exomes 𝑓: 1.0 (724053 hom.)
• Consequence: FMO2 NM_001460.5 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.91

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 -8 ACMG points.

• PM4: Stoplost variant in NM_001460.5 Downstream stopcodon found after 557 codons.
• BP6: Variant 1-171208951-C-T is Benign according to our data. Variant chr1-171208951-C-T is described in ClinVar as [Benign]. Clinvar id is 769222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO2	NM_001460.5	c.1414C>T	p.Gln472Ter	stop_gained	9/9	ENST00000209929.10
LOC124900413	XR_007066731.1	n.366-12013G>A		intron_variant, non_coding_transcript_variant
LOC105371611	XR_922278.4	n.514+38630G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMO2	ENST00000209929.10	c.1414C>T	p.Gln472Ter	stop_gained	9/9	1	NM_001460.5	P1
	ENST00000445290.1	n.139-9436G>A		intron_variant, non_coding_transcript_variant		2
	ENST00000669750.1	n.448+38615G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146637 AN: 152068 Hom.: 70918 Cov.: 31

Gnomad AFR AF: 0.879

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.974

GnomAD4 exome AF: 0.995 AC: 1454424 AN: 1461402 Hom.: 724053 Cov.: 45 AF XY: 0.995 AC XY: 723575 AN XY: 726990

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.992

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.989

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.989

GnomAD4 genome AF: 0.964 AC: 146712 AN: 152186 Hom.: 70946 Cov.: 31 AF XY: 0.965 AC XY: 71793 AN XY: 74394

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.985

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.989

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.974

Alfa AF: 0.992 Hom.: 174166

Bravo AF: 0.960

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Pathogenic	40
Vest4		0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6661174; hg19: chr1-171178090;