1-147185664-C-T

Position:

• chr1-147185664-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348451.2(CHD1L):​c.-90+11079C>T 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: CHD1L NM_001348451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

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]

ENSG00000237188 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1L	NM_001348451.2	c.-90+11079C>T		intron_variant			NP_001335380.1
FMO5	NM_001144829.3	c.1257-1034G>A		intron_variant			NP_001138301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMO5	ENST00000441068.6	c.1257-1034G>A		intron_variant		1		ENSP00000416011.2
FMO5	ENST00000578284.5	c.1257-1034G>A		intron_variant		5		ENSP00000462062.2
FMO5	ENST00000527849.5	n.*258+4513G>A		intron_variant		5		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

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0336

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0247

Gnomad4 NFE AF: 0.00378

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0106 Hom.: 54

Bravo AF: 0.0449

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6690158; hg19: chr1-146657243;