rs6661174

Variant names:

• chr1-171208951-C-T
• rs6661174
• NM_001460.5:c.1414C>T

Variant summary

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

The NM_001460.5(FMO2):​c.1414C>T​(p.Gln472*) 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
• Publications: 23 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-171208951-C-T is Benign according to our data. Variant chr1-171208951-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.1414C>T	p.Gln472*	stop_gained	Exon 9 of 9	NP_001451.2	Q99518
	FMO2	NM_001365900.2		c.1219C>T	p.Gln407*	stop_gained	Exon 8 of 8	NP_001352829.1
	FMO2	NM_001301347.2		c.754C>T	p.Gln252*	stop_gained	Exon 7 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.1414C>T	p.Gln472*	stop_gained	Exon 9 of 9	ENSP00000209929.8	Q99518
	FMO2	ENST00000895514.1		c.1414C>T	p.Gln472*	stop_gained	Exon 9 of 9	ENSP00000565573.1
	FMO2	ENST00000895513.1		c.1411C>T	p.Gln471*	stop_gained	Exon 9 of 9	ENSP00000565572.1

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

African (AFR) AF: 0.875 AC: 29243 AN: 33436

American (AMR) AF: 0.992 AC: 44327 AN: 44704

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26113 AN: 26114

East Asian (EAS) AF: 1.00 AC: 39677 AN: 39678

South Asian (SAS) AF: 0.989 AC: 85234 AN: 86178

European-Finnish (FIN) AF: 1.00 AC: 53418 AN: 53418

Middle Eastern (MID) AF: 0.978 AC: 5631 AN: 5760

European-Non Finnish (NFE) AF: 0.999 AC: 1111050 AN: 1111730

Other (OTH) AF: 0.989 AC: 59731 AN: 60384

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

African (AFR) AF: 0.878 AC: 36430 AN: 41498

American (AMR) AF: 0.985 AC: 15048 AN: 15280

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5162 AN: 5162

South Asian (SAS) AF: 0.989 AC: 4772 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10608 AN: 10608

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67959 AN: 68018

Other (OTH) AF: 0.974 AC: 2061 AN: 2116

Alfa AF: 0.989 Hom.: 339744

Bravo AF: 0.960

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	40
PhyloP100		7.9
Vest4		0.56

Splicing

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

Other links and lift over

dbSNP: rs6661174; hg19: chr1-171178090;