NM_004284.6:c.39C>G

Variant names:

• chr1-147242742-C-G
• rs1890042
• NM_004284.6:c.39C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004284.6(CHD1L):​c.39C>G​(p.Ala13Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,261,044 control chromosomes in the GnomAD database, including 19,634 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. Synonymous variant affecting the same amino acid position (i.e. A13A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.22 (4683 hom., cov: 33)
  • Exomes 𝑓: 0.15 (14951 hom.)
• Consequence: CHD1L NM_004284.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.991
• Publications: 14 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.991 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004284.6. 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
	CHD1L	NM_004284.6	MANE Select	c.39C>G	p.Ala13Ala	synonymous	Exon 1 of 23	NP_004275.4
	CHD1L	NM_001348454.2		c.39C>G	p.Ala13Ala	synonymous	Exon 1 of 18	NP_001335383.1	A0A0A0MRH8
	CHD1L	NM_001256338.3		c.39C>G	p.Ala13Ala	synonymous	Exon 1 of 17	NP_001243267.1	Q86WJ1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1L	ENST00000369258.8	TSL:1 MANE Select	c.39C>G	p.Ala13Ala	synonymous	Exon 1 of 23	ENSP00000358262.4	Q86WJ1-1
	CHD1L	ENST00000369259.4	TSL:1	c.39C>G	p.Ala13Ala	synonymous	Exon 1 of 17	ENSP00000358263.3	Q86WJ1-3
	CHD1L	ENST00000467213.5	TSL:1	n.39C>G		non_coding_transcript_exon	Exon 1 of 21	ENSP00000477985.1	A0A087WTM4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34065 AN: 151950 Hom.: 4664 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.152 AC: 168307 AN: 1108986 Hom.: 14951 Cov.: 35 AF XY: 0.151 AC XY: 79186 AN XY: 525590

African (AFR) AF: 0.401 AC: 9539 AN: 23808

American (AMR) AF: 0.194 AC: 1980 AN: 10208

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 2097 AN: 14478

East Asian (EAS) AF: 0.394 AC: 10918 AN: 27684

South Asian (SAS) AF: 0.175 AC: 3650 AN: 20836

European-Finnish (FIN) AF: 0.192 AC: 6652 AN: 34652

Middle Eastern (MID) AF: 0.129 AC: 509 AN: 3944

European-Non Finnish (NFE) AF: 0.135 AC: 124953 AN: 928938

Other (OTH) AF: 0.180 AC: 8009 AN: 44438

GnomAD4 genome AF: 0.224 AC: 34122 AN: 152058 Hom.: 4683 Cov.: 33 AF XY: 0.225 AC XY: 16749 AN XY: 74332

African (AFR) AF: 0.390 AC: 16176 AN: 41502

American (AMR) AF: 0.185 AC: 2824 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3468

East Asian (EAS) AF: 0.342 AC: 1758 AN: 5136

South Asian (SAS) AF: 0.183 AC: 880 AN: 4818

European-Finnish (FIN) AF: 0.195 AC: 2067 AN: 10602

Middle Eastern (MID) AF: 0.141 AC: 41 AN: 290

European-Non Finnish (NFE) AF: 0.139 AC: 9425 AN: 67932

Other (OTH) AF: 0.185 AC: 390 AN: 2110

Alfa AF: 0.0751 Hom.: 207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
PhyloP100		0.99
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1890042; hg19: chr1-146714392;