rs372889781
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_017780.4(CHD7):c.8718C>T(p.Ser2906=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,608,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
CHD7
NM_017780.4 synonymous
NM_017780.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.34
Genes affected
CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 8-60865657-C-T is Benign according to our data. Variant chr8-60865657-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.34 with no splicing effect.
BS2
?
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.8718C>T | p.Ser2906= | synonymous_variant | 38/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.8718C>T | p.Ser2906= | synonymous_variant | 38/38 | 5 | NM_017780.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152220Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
11
AN:
152220
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000648 AC: 16AN: 246902Hom.: 0 AF XY: 0.0000896 AC XY: 12AN XY: 133990
GnomAD3 exomes
AF:
AC:
16
AN:
246902
Hom.:
AF XY:
AC XY:
12
AN XY:
133990
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: 0.000152 AC: 222AN: 1456320Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 108AN XY: 723614
GnomAD4 exome
AF:
AC:
222
AN:
1456320
Hom.:
Cov.:
31
AF XY:
AC XY:
108
AN XY:
723614
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 ? AF: 0.0000723 AC: 11AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74360
GnomAD4 genome
?
AF:
AC:
11
AN:
152220
Hom.:
Cov.:
33
AF XY:
AC XY:
7
AN XY:
74360
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 04, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2017 | p.Ser2906Ser in exon 38 of CHD7: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.01% (4/66274) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs372889781). - |
CHARGE syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
CHD7-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 29, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | CHD7: BP4, BP7 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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