chrX-110694315-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001143981.2(CHRDL1):c.626G>A(p.Arg209His) variant causes a missense change. The variant allele was found at a frequency of 0.00207 in 1,202,666 control chromosomes in the GnomAD database, including 21 homozygotes. There are 720 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0092 ( 10 hom., 297 hem., cov: 22)
Exomes 𝑓: 0.0013 ( 11 hom. 423 hem. )
Consequence
CHRDL1
NM_001143981.2 missense
NM_001143981.2 missense
Scores
1
3
12
Clinical Significance
Conservation
PhyloP100: 3.91
Genes affected
CHRDL1 (HGNC:29861): (chordin like 1) This gene encodes an antagonist of bone morphogenetic protein 4. The encoded protein may play a role in topographic retinotectal projection and in the regulation of retinal angiogenesis in response to hypoxia. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009160072).
BP6
Variant X-110694315-C-T is Benign according to our data. Variant chrX-110694315-C-T is described in ClinVar as [Benign]. Clinvar id is 788059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00916 (1023/111669) while in subpopulation AFR AF= 0.0291 (893/30727). AF 95% confidence interval is 0.0275. There are 10 homozygotes in gnomad4. There are 297 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRDL1 | NM_001143981.2 | c.626G>A | p.Arg209His | missense_variant | 8/12 | ENST00000372042.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRDL1 | ENST00000372042.6 | c.626G>A | p.Arg209His | missense_variant | 8/12 | 2 | NM_001143981.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00914 AC: 1020AN: 111619Hom.: 10 Cov.: 22 AF XY: 0.00869 AC XY: 294AN XY: 33833
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GnomAD3 exomes AF: 0.00379 AC: 673AN: 177767Hom.: 6 AF XY: 0.00271 AC XY: 170AN XY: 62633
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GnomAD4 exome AF: 0.00134 AC: 1465AN: 1090997Hom.: 11 Cov.: 29 AF XY: 0.00119 AC XY: 423AN XY: 356739
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GnomAD4 genome AF: 0.00916 AC: 1023AN: 111669Hom.: 10 Cov.: 22 AF XY: 0.00876 AC XY: 297AN XY: 33893
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 2018 | - - |
CHRDL1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 12, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.;.;.;.
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.
MutationTaster
Benign
P;P;P;P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
D;.;.;.;.
Vest4
MVP
MPC
1.2
ClinPred
T
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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