chr14-21385738-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001170629.2(CHD8):c.7621G>A(p.Asp2541Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000114 in 1,399,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
CHD8
NM_001170629.2 missense
NM_001170629.2 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 4.12
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CHD8
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15173349).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD8 | NM_001170629.2 | c.7621G>A | p.Asp2541Asn | missense_variant | 38/38 | ENST00000646647.2 | |
LOC107984643 | XR_001750627.2 | n.441+1025C>T | intron_variant, non_coding_transcript_variant | ||||
CHD8 | NM_020920.4 | c.6784G>A | p.Asp2262Asn | missense_variant | 38/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD8 | ENST00000646647.2 | c.7621G>A | p.Asp2541Asn | missense_variant | 38/38 | NM_001170629.2 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD3 exomes AF: 0.00000635 AC: 1AN: 157480Hom.: 0 AF XY: 0.0000120 AC XY: 1AN XY: 83150
GnomAD3 exomes
AF:
AC:
1
AN:
157480
Hom.:
AF XY:
AC XY:
1
AN XY:
83150
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000114 AC: 16AN: 1399564Hom.: 0 Cov.: 35 AF XY: 0.00000869 AC XY: 6AN XY: 690294
GnomAD4 exome
AF:
AC:
16
AN:
1399564
Hom.:
Cov.:
35
AF XY:
AC XY:
6
AN XY:
690294
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 30
GnomAD4 genome
?
Cov.:
30
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
0
ExAC
?
AF:
AC:
1
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 | Jan 05, 2019 | The p.D2541N variant (also known as c.7621G>A), located in coding exon 37 of the CHD8 gene, results from a G to A substitution at nucleotide position 7621. The aspartic acid at codon 2541 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;.;N;.
REVEL
Benign
Sift
Uncertain
D;D;.;.;D;.
Sift4G
Benign
T;T;.;.;T;.
Polyphen
P;.;.;P;.;.
Vest4
MutPred
0.12
.;Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP
MPC
0.29
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at