Variant 1-147242742-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004284.6(CHD1L):c.39C>T(p.Ala13Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,261,030 control chromosomes in the GnomAD database, including 34,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3541 hom., cov: 33)

Exomes 𝑓: 0.23 ( 30905 hom. )

Consequence

CHD1L
NM_004284.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.991

Variant links:

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]

CHD1L links:

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 links:

ENSG00000237188 (HGNC:):

ENSG00000237188 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-147242742-C-T is Benign according to our data. Variant chr1-147242742-C-T is described in ClinVar as [Benign]. Clinvar id is 1273099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.991 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1L	NM_004284.6 link	c.39C>T	p.Ala13Ala	synonymous_variant	1/23	ENST00000369258.8	NP_004275.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD1L	ENST00000369258.8 link	c.39C>T	p.Ala13Ala	synonymous_variant	1/23	1	NM_004284.6	ENSP00000358262.4		Q86WJ1-1

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31940

AN:

151946

Hom.:

3542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.233

AC:

258794

AN:

1108976

Hom.:

30905

Cov.:

AF XY:

0.234

AC XY:

123078

AN XY:

525584

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.0864

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.210

AC:

31947

AN:

152054

Hom.:

3541

Cov.:

AF XY:

0.212

AC XY:

15740

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.248

Gnomad4 NFE

AF:

0.240

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.149

Hom.:

207

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over