chr1-6106500-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_015557.3(CHD5):c.5752G>C(p.Gly1918Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000876 in 1,552,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )
Consequence
CHD5
NM_015557.3 missense
NM_015557.3 missense
Scores
2
13
4
Clinical Significance
Conservation
PhyloP100: 5.46
Genes affected
CHD5 (HGNC:16816): (chromodomain helicase DNA binding protein 5) This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CHD5
BS2
?
High AC in GnomAd at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD5 | NM_015557.3 | c.5752G>C | p.Gly1918Arg | missense_variant | 40/42 | ENST00000262450.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD5 | ENST00000262450.8 | c.5752G>C | p.Gly1918Arg | missense_variant | 40/42 | 1 | NM_015557.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000159 AC: 25AN: 157618Hom.: 0 AF XY: 0.000144 AC XY: 12AN XY: 83330
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GnomAD4 exome AF: 0.0000879 AC: 123AN: 1399898Hom.: 0 Cov.: 34 AF XY: 0.0000825 AC XY: 57AN XY: 690744
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74322
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2023 | The c.5752G>C (p.G1918R) alteration is located in exon 40 (coding exon 40) of the CHD5 gene. This alteration results from a G to C substitution at nucleotide position 5752, causing the glycine (G) at amino acid position 1918 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -12
Find out detailed SpliceAI scores and Pangolin per-transcript scores at