chr1-147264552-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004284.6(CHD1L):​c.707G>A​(p.Arg236His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

CHD1L
NM_004284.6 missense

Scores

12

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.323

Publications

8 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]
LINC00624 (HGNC:44254): (long intergenic non-protein coding RNA 624)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.012054473).
BS2
High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHD1LNM_004284.6 linkc.707G>A p.Arg236His missense_variant Exon 7 of 23 ENST00000369258.8 NP_004275.4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHD1LENST00000369258.8 linkc.707G>A p.Arg236His missense_variant Exon 7 of 23 1 NM_004284.6 ENSP00000358262.4 Q86WJ1-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152086
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00230
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000195
AC:
49
AN:
251016
AF XY:
0.000170
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00308
Gnomad EAS exome
AF:
0.000218
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000876
AC:
128
AN:
1461580
Hom.:
0
Cov.:
31
AF XY:
0.0000729
AC XY:
53
AN XY:
727074
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33456
American (AMR)
AF:
0.000134
AC:
6
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
0.00302
AC:
79
AN:
26126
East Asian (EAS)
AF:
0.0000756
AC:
3
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86188
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000225
AC:
25
AN:
1111872
Other (OTH)
AF:
0.000232
AC:
14
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
7
13
20
26
33
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:
0.0000723
AC:
11
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74430
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41520
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00230
AC:
8
AN:
3472
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4812
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68006
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.511
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:
0.000176
Hom.:
0
Bravo
AF:
0.0000982
ExAC
AF:
0.000165
AC:
20
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1
Oct 01, 2018
CeGaT Center for Human Genetics Tuebingen
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Congenital anomaly of kidney and urinary tract Uncertain:1
-
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.056
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
15
DANN
Benign
0.51
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.012
T
MetaSVM
Benign
-0.31
T
PhyloP100
0.32
ClinPred
0.024
T
GERP RS
4.4
Varity_R
0.040
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs201333837; hg19: chr1-146736211; COSMIC: COSV63614837; COSMIC: COSV63614837; API