1-147242803-C-G

Variant names:

• chr1-147242803-C-G
• rs1368853275
• NM_004284.6:c.100C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004284.6(CHD1L):​c.100C>G​(p.Gln34Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 1,124,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q34K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CHD1L NM_004284.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1289168).

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.100C>G	p.Gln34Glu	missense	Exon 1 of 23	NP_004275.4
	CHD1L	NM_001348454.2		c.100C>G	p.Gln34Glu	missense	Exon 1 of 18	NP_001335383.1	A0A0A0MRH8
	CHD1L	NM_001256338.3		c.100C>G	p.Gln34Glu	missense	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.100C>G	p.Gln34Glu	missense	Exon 1 of 23	ENSP00000358262.4	Q86WJ1-1
	CHD1L	ENST00000369259.4	TSL:1	c.100C>G	p.Gln34Glu	missense	Exon 1 of 17	ENSP00000358263.3	Q86WJ1-3
	CHD1L	ENST00000467213.5	TSL:1	n.100C>G		non_coding_transcript_exon	Exon 1 of 21	ENSP00000477985.1	A0A087WTM4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000178 AC: 2 AN: 1124700 Hom.: 0 Cov.: 32 AF XY: 0.00000374 AC XY: 2 AN XY: 534782

African (AFR) AF: 0.00 AC: 0 AN: 24350

American (AMR) AF: 0.00 AC: 0 AN: 11670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14618

East Asian (EAS) AF: 0.00 AC: 0 AN: 28796

South Asian (SAS) AF: 0.0000920 AC: 2 AN: 21740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4478

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 936582

Other (OTH) AF: 0.00 AC: 0 AN: 44972

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.42	N
PhyloP100		0.88
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.62		Gain of loop (P = 0.024)
MVP		0.72
MPC		0.040
ClinPred		0.084	T
GERP RS		2.0
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.4
Varity_R		0.15
gMVP		0.26
Mutation Taster		=92/8	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: rs1368853275; hg19: chr1-146714453;