chr5-98858214-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001270.4(CHD1):c.4753C>T(p.His1585Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CHD1
NM_001270.4 missense
NM_001270.4 missense
Scores
6
5
4
Clinical Significance
Conservation
PhyloP100: 9.02
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
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.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD1 | NM_001270.4 | c.4753C>T | p.His1585Tyr | missense_variant | 35/36 | ENST00000614616.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD1 | ENST00000614616.5 | c.4753C>T | p.His1585Tyr | missense_variant | 35/36 | 5 | NM_001270.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151910Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251166Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135762
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460984Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726806
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151910Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74196
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pilarowski-Bjornsson syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 24, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Gain of phosphorylation at H1585 (P = 0.0062);Gain of phosphorylation at H1585 (P = 0.0062);
MVP
MPC
0.046
ClinPred
D
GERP RS
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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