chr14-21385694-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001170629.2(CHD8):c.7665T>C(p.Asp2555=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,551,912 control chromosomes in the GnomAD database, including 423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.016 ( 24 hom., cov: 31)
Exomes 𝑓: 0.023 ( 399 hom. )
Consequence
CHD8
NM_001170629.2 synonymous
NM_001170629.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.22
Genes affected
CHD8 (HGNC:20153): (chromodomain helicase DNA binding protein 8) This gene encodes a member of the chromodomain-helicase-DNA binding protein family, which is characterized by a SNF2-like domain and two chromatin organization modifier domains. The encoded protein also contains brahma and kismet domains, which are common to the subfamily of chromodomain-helicase-DNA binding proteins to which this protein belongs. This gene has been shown to function in several processes that include transcriptional regulation, epigenetic remodeling, promotion of cell proliferation, and regulation of RNA synthesis. Allelic variants of this gene are associated with autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 14-21385694-A-G is Benign according to our data. Variant chr14-21385694-A-G is described in ClinVar as [Benign]. Clinvar id is 587884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-21385694-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.22 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0158 (2412/152210) while in subpopulation NFE AF= 0.0256 (1744/67996). AF 95% confidence interval is 0.0246. There are 24 homozygotes in gnomad4. There are 1130 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 2412 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD8 | NM_001170629.2 | c.7665T>C | p.Asp2555= | synonymous_variant | 38/38 | ENST00000646647.2 | |
LOC107984643 | XR_001750627.2 | n.441+981A>G | intron_variant, non_coding_transcript_variant | ||||
CHD8 | NM_020920.4 | c.6828T>C | p.Asp2276= | synonymous_variant | 38/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD8 | ENST00000646647.2 | c.7665T>C | p.Asp2555= | synonymous_variant | 38/38 | NM_001170629.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0159 AC: 2412AN: 152092Hom.: 24 Cov.: 31
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GnomAD3 exomes AF: 0.0163 AC: 2577AN: 158224Hom.: 31 AF XY: 0.0156 AC XY: 1302AN XY: 83362
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GnomAD4 exome AF: 0.0231 AC: 32283AN: 1399702Hom.: 399 Cov.: 35 AF XY: 0.0227 AC XY: 15639AN XY: 690332
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 14, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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