5-98856391-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_001270.4(CHD1):c.5122C>T(p.Arg1708Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000192 in 1,606,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
CHD1
NM_001270.4 missense
NM_001270.4 missense
Scores
3
12
4
Clinical Significance
Conservation
PhyloP100: 7.18
Genes affected
CHD1 (HGNC:1915): (chromodomain helicase DNA binding protein 1) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CHD1. . Trascript score misZ 3.2778 (greater than threshold 3.09). GenCC has associacion of gene with Pilarowski-Bjornsson syndrome.
BS2
High AC in GnomAd4 at 32 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHD1 | NM_001270.4 | c.5122C>T | p.Arg1708Trp | missense_variant | 36/36 | ENST00000614616.5 | NP_001261.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHD1 | ENST00000614616.5 | c.5122C>T | p.Arg1708Trp | missense_variant | 36/36 | 5 | NM_001270.4 | ENSP00000483667 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152024Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000184 AC: 46AN: 250424Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135404
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GnomAD4 exome AF: 0.000190 AC: 277AN: 1454816Hom.: 0 Cov.: 30 AF XY: 0.000201 AC XY: 145AN XY: 722496
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GnomAD4 genome AF: 0.000210 AC: 32AN: 152024Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74254
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2021 | The c.5122C>T (p.R1708W) alteration is located in exon 35 (coding exon 35) of the CHD1 gene. This alteration results from a C to T substitution at nucleotide position 5122, causing the arginine (R) at amino acid position 1708 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Clinical Genetics Laboratory, Skane University Hospital Lund | Sep 21, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D
REVEL
Uncertain
Sift
Uncertain
.;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
0.13
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at