NM_004284.6:c.36A>G

Variant names:

• chr1-147242739-A-G
• rs587765929
• NM_004284.6:c.36A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_004284.6(CHD1L):​c.36A>G​(p.Gln12Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000628 in 1,261,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: CHD1L NM_004284.6 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.967
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-147242739-A-G is Benign according to our data. Variant chr1-147242739-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3051556.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.967 with no splicing effect.
• BS2: High AC in GnomAd4 at 75 AD gene.

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.36A>G	p.Gln12Gln	synonymous	Exon 1 of 23	NP_004275.4
	CHD1L	NM_001348454.2		c.36A>G	p.Gln12Gln	synonymous	Exon 1 of 18	NP_001335383.1	A0A0A0MRH8
	CHD1L	NM_001256338.3		c.36A>G	p.Gln12Gln	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.36A>G	p.Gln12Gln	synonymous	Exon 1 of 23	ENSP00000358262.4	Q86WJ1-1
	CHD1L	ENST00000369259.4	TSL:1	c.36A>G	p.Gln12Gln	synonymous	Exon 1 of 17	ENSP00000358263.3	Q86WJ1-3
	CHD1L	ENST00000467213.5	TSL:1	n.36A>G		non_coding_transcript_exon	Exon 1 of 21	ENSP00000477985.1	A0A087WTM4

Frequencies

GnomAD3 genomes AF: 0.000494 AC: 75 AN: 151940 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000325 AC: 11 AN: 33834 AF XY: 0.000278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000505

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000615

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000646 AC: 717 AN: 1109918 Hom.: 0 Cov.: 31 AF XY: 0.000690 AC XY: 363 AN XY: 526278

African (AFR) AF: 0.0000419 AC: 1 AN: 23866

American (AMR) AF: 0.000774 AC: 8 AN: 10338

Ashkenazi Jewish (ASJ) AF: 0.000690 AC: 10 AN: 14486

East Asian (EAS) AF: 0.00 AC: 0 AN: 27710

South Asian (SAS) AF: 0.00 AC: 0 AN: 20916

European-Finnish (FIN) AF: 0.0000868 AC: 3 AN: 34580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3940

European-Non Finnish (NFE) AF: 0.000730 AC: 679 AN: 929604

Other (OTH) AF: 0.000360 AC: 16 AN: 44478

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152050 Hom.: 0 Cov.: 33 AF XY: 0.000430 AC XY: 32 AN XY: 74338

African (AFR) AF: 0.0000723 AC: 3 AN: 41484

American (AMR) AF: 0.000719 AC: 11 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000854 AC: 58 AN: 67950

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000688 Hom.: 0

Bravo AF: 0.000650

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CHD1L-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.27
PhyloP100		-0.97
PromoterAI		0.24	Neutral
Mutation Taster		=297/3	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: rs587765929; hg19: chr1-146714389;