rs11588753

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004284.6(CHD1L):​c.74G>A​(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000575 in 1,269,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

CHD1L
NM_004284.6 missense

Scores

2
17

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]
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08832684).
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHD1LNM_004284.6 linkc.74G>A p.Arg25Gln missense_variant Exon 1 of 23 ENST00000369258.8 NP_004275.4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHD1LENST00000369258.8 linkc.74G>A p.Arg25Gln missense_variant Exon 1 of 23 1 NM_004284.6 ENSP00000358262.4 Q86WJ1-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152128
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000228
AC:
1
AN:
43920
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000358
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
0.0000581
AC:
65
AN:
1117846
Hom.:
0
Cov.:
33
AF XY:
0.0000603
AC XY:
32
AN XY:
530606
show subpopulations
African (AFR)
AF:
0.0000829
AC:
2
AN:
24112
American (AMR)
AF:
0.0000911
AC:
1
AN:
10972
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14562
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28348
South Asian (SAS)
AF:
0.00
AC:
0
AN:
21334
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36816
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4394
European-Non Finnish (NFE)
AF:
0.0000536
AC:
50
AN:
932606
Other (OTH)
AF:
0.000268
AC:
12
AN:
44702
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.476
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152128
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74316
show subpopulations
African (AFR)
AF:
0.0000965
AC:
4
AN:
41442
American (AMR)
AF:
0.0000654
AC:
1
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
67996
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
34
ExAC
AF:
0.0000186
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
17
DANN
Benign
0.93
DEOGEN2
Benign
0.0076
T;.
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.066
N
LIST_S2
Benign
0.66
T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.088
T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
0.69
N;N
PhyloP100
0.77
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
0.040
N;N
REVEL
Benign
0.23
Sift
Benign
0.20
T;T
Sift4G
Benign
0.40
T;T
Polyphen
0.30
B;B
Vest4
0.096
MutPred
0.55
Loss of MoRF binding (P = 0.0643);Loss of MoRF binding (P = 0.0643);
MVP
0.81
MPC
0.042
ClinPred
0.11
T
GERP RS
3.1
PromoterAI
-0.063
Neutral
Varity_R
0.11
gMVP
0.28
Mutation Taster
=98/2
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

Publications

Other links and lift over

dbSNP: rs11588753; hg19: chr1-146714427; API