Genetic Variant CHD1L:p.Arg25Leu (chr1-147242777-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004284.6(CHD1L):c.74G>T(p.Arg25Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R25P) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHD1L
NM_004284.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.773

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

FMO5 links:

ENSG00000237188 (HGNC:):

ENSG00000237188 links:

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ACMG classification

Classification was made for transcript

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=0.1908887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD1L	NM_004284.6 link	c.74G>T	p.Arg25Leu	missense_variant	Exon 1 of 23	ENST00000369258.8	NP_004275.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD1L	ENST00000369258.8 link	c.74G>T	p.Arg25Leu	missense_variant	Exon 1 of 23	1	NM_004284.6	ENSP00000358262.4		Q86WJ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1117846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

530606

African (AFR)

AF:

0.00

AC:

AN:

24112

American (AMR)

AF:

0.00

AC:

AN:

10972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14562

East Asian (EAS)

AF:

0.00

AC:

AN:

28348

South Asian (SAS)

AF:

0.00

AC:

AN:

21334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4394

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

932606

Other (OTH)

AF:

0.00

AC:

AN:

44702

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

0.0014

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0070

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.74

T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.0

L;L

PhyloP100

0.77

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.20

Sift

Benign

0.086

T;T

Sift4G

Benign

0.099

T;T

Polyphen

0.089

B;B

Vest4

0.30

MutPred

0.57

Loss of solvent accessibility (P = 0.0364);Loss of solvent accessibility (P = 0.0364);

MVP

0.52

MPC

0.055

ClinPred

0.26

GERP RS

3.1

PromoterAI

0.18

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.18

gMVP

0.38

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over