dbSNP rs587765929: CHD1L:p.Gln12His (chr1-147242739-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004284.6(CHD1L):c.36A>C(p.Gln12His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000901 in 1,109,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. Q12R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

CHD1L
NM_004284.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.967

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062033743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD1L	NM_004284.6 link	c.36A>C	p.Gln12His	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.36A>C	p.Gln12His	missense_variant	Exon 1 of 23	1	NM_004284.6	ENSP00000358262.4		Q86WJ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000296

AC:

AN:

33834

Hom.:

AF XY:

0.00

AC XY:

AN XY:

17958

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.01e-7

AC:

AN:

1109918

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

526278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000964

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

2.0

DANN

Benign

0.74

DEOGEN2

Benign

0.0096

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.34

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.17

N;N

REVEL

Benign

0.16

Sift

Benign

0.22

T;D

Sift4G

Benign

0.18

T;.

Polyphen

0.0

B;B

Vest4

0.14

MutPred

0.27

Gain of glycosylation at S8 (P = 0.0871);Gain of glycosylation at S8 (P = 0.0871);

MVP

0.15

MPC

0.037

ClinPred

0.044

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.032

gMVP

0.41

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over