chr1-147177485-A-G

Variant names:

• chr1-147177485-A-G
• rs7525703
• NM_001348451.2:c.-90+2900A>G

Variant summary

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

The NM_001348451.2(CHD1L):​c.-90+2900A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,956 control chromosomes in the GnomAD database, including 10,968 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 0.37 (10968 hom., cov: 31)
• Consequence: CHD1L NM_001348451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 7 publications found

Genes affected

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]

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]

FMO5 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348451.2. 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+2900A>G		intron	N/A	NP_001335380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO5	ENST00000527849.5	TSL:5	n.*259-1095T>C		intron	N/A	ENSP00000433742.1
	ENSG00000237188	ENST00000606757.1	TSL:3	n.258+2900A>G		intron	N/A
	ENSG00000237188	ENST00000606856.1	TSL:5	n.536+2900A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56557 AN: 151836 Hom.: 10950 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.324

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.373 AC: 56612 AN: 151956 Hom.: 10968 Cov.: 31 AF XY: 0.372 AC XY: 27618 AN XY: 74280

African (AFR) AF: 0.496 AC: 20543 AN: 41414

American (AMR) AF: 0.339 AC: 5178 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1532 AN: 5164

South Asian (SAS) AF: 0.400 AC: 1917 AN: 4798

European-Finnish (FIN) AF: 0.321 AC: 3389 AN: 10568

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21908 AN: 67946

Other (OTH) AF: 0.353 AC: 746 AN: 2112

Alfa AF: 0.262 Hom.: 940

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs7525703; hg19: chr1-146649064;