1-171196723-C-T

Variant names:

• chr1-171196723-C-T
• rs41272515
• NM_001460.5:c.396C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001301347.2(FMO2):​c.-122C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: FMO2 NM_001301347.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.74
• Publications: 2 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]

LOC124900413 (HGNC:):

FMO1-AS1 (HGNC:40240):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-171196723-C-T is Benign according to our data. Variant chr1-171196723-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 724168.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301347.2. 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.396C>T	p.Asn132Asn	synonymous	Exon 4 of 9	NP_001451.2	Q99518
	FMO2	NM_001301347.2		c.-122C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_001288276.1
	FMO2	NM_001365900.2		c.201C>T	p.Asn67Asn	synonymous	Exon 3 of 8	NP_001352829.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO2	ENST00000209929.10	TSL:1 MANE Select	c.396C>T	p.Asn132Asn	synonymous	Exon 4 of 9	ENSP00000209929.8	Q99518
	FMO2	ENST00000895514.1		c.396C>T	p.Asn132Asn	synonymous	Exon 4 of 9	ENSP00000565573.1
	FMO2	ENST00000895513.1		c.393C>T	p.Asn131Asn	synonymous	Exon 4 of 9	ENSP00000565572.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000836 AC: 21 AN: 251196 AF XY: 0.000103

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000404 AC: 59 AN: 1461276 Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23 AN XY: 726952

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86222

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111808

Other (OTH) AF: 0.0000497 AC: 3 AN: 60344

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74482

African (AFR) AF: 0.0000722 AC: 3 AN: 41568

American (AMR) AF: 0.000327 AC: 5 AN: 15290

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000124 Hom.: 0

Bravo AF: 0.000181

ClinVar

ClinVar submissions

Significance: Likely 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	-0.70
CADD	Benign	1.6
DANN	Benign	0.80
PhyloP100		-8.7
Mutation Taster		=100/0	polymorphism

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: rs41272515; hg19: chr1-171165862; COSMIC: COSV52951029; COSMIC: COSV52951029;