Variant 1-147242750-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004284.6(CHD1L):c.47T>A(p.Phe16Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000359 in 1,113,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CHD1L
NM_004284.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12831292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD1L	NM_004284.6 linkuse as main transcript	c.47T>A	p.Phe16Tyr	missense_variant	1/23	ENST00000369258.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD1L	ENST00000369258.8 linkuse as main transcript	c.47T>A	p.Phe16Tyr	missense_variant	1/23	1	NM_004284.6	P1	Q86WJ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000102

AC:

AN:

39254

Hom.:

AF XY:

0.0000971

AC XY:

AN XY:

20606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00158

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000359

AC:

AN:

1113170

Hom.:

Cov.:

AF XY:

0.00000189

AC XY:

AN XY:

527992

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000143

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000470

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.47T>A (p.F16Y) alteration is located in exon 1 (coding exon 1) of the CHD1L gene. This alteration results from a T to A substitution at nucleotide position 47, causing the phenylalanine (F) at amino acid position 16 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0059

T;.

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.55

T;T

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.13

T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.29

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.59

T;.

Polyphen

0.98

D;D

Vest4

0.50

MutPred

0.24

Gain of phosphorylation at F16 (P = 0.0615);Gain of phosphorylation at F16 (P = 0.0615);

MVP

0.78

MPC

0.28

ClinPred

0.39

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.13

gMVP

0.45

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