1-147185664-C-T

Variant names:

• chr1-147185664-C-T
• rs6690158
• ENST00000441068.6:c.1257-1034G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441068.6(FMO5):​c.1257-1034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 152,220 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.041 (303 hom., cov: 32)
• Consequence: FMO5 ENST00000441068.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 4 publications found

Genes affected

FMO5 (HGNC:3773): (flavin containing dimethylaniline monoxygenase 5) Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

CHD1L (HGNC:1916): (chromodomain helicase DNA binding protein 1 like) This gene encodes a DNA helicase protein involved in DNA repair. The protein converts ATP to add poly(ADP-ribose) as it regulates chromatin relaxation following DNA damage. Overexpression of this gene has been linked to several types of cancers. [provided by RefSeq, Feb 2017]

CHD1L Gene-Disease associations (from GenCC):

• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000237188 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441068.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1L	NM_001348451.2		c.-90+11079C>T		intron	N/A	NP_001335380.1
	FMO5	NM_001144829.3		c.1257-1034G>A		intron	N/A	NP_001138301.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO5	ENST00000441068.6	TSL:1	c.1257-1034G>A		intron	N/A	ENSP00000416011.2
	FMO5	ENST00000578284.5	TSL:5	c.1257-1034G>A		intron	N/A	ENSP00000462062.2
	FMO5	ENST00000527849.5	TSL:5	n.*258+4513G>A		intron	N/A	ENSP00000433742.1

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6274 AN: 152102 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00379

Gnomad OTH AF: 0.0330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0413 AC: 6286 AN: 152220 Hom.: 303 Cov.: 32 AF XY: 0.0417 AC XY: 3106 AN XY: 74424

African (AFR) AF: 0.102 AC: 4218 AN: 41516

American (AMR) AF: 0.0336 AC: 514 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.167 AC: 867 AN: 5178

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4826

European-Finnish (FIN) AF: 0.0247 AC: 262 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00378 AC: 257 AN: 68010

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0144 Hom.: 117

Bravo AF: 0.0449

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.48
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6690158; hg19: chr1-146657243;