rs556577614
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_017780.4(CHD7):c.6669C>T(p.Val2223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,536,620 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
CHD7
NM_017780.4 synonymous
NM_017780.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.696
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 8-60853394-C-T is Benign according to our data. Variant chr8-60853394-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 459560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.696 with no splicing effect.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.6669C>T | p.Val2223= | synonymous_variant | 31/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.6669C>T | p.Val2223= | synonymous_variant | 31/38 | 5 | NM_017780.4 | P1 | |
CHD7 | ENST00000524602.5 | c.1717-8835C>T | intron_variant | 1 | |||||
CHD7 | ENST00000695853.1 | c.6669C>T | p.Val2223= | synonymous_variant, NMD_transcript_variant | 31/37 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000162 AC: 3AN: 184910Hom.: 0 AF XY: 0.0000204 AC XY: 2AN XY: 98254
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GnomAD4 exome AF: 0.0000195 AC: 27AN: 1384360Hom.: 0 Cov.: 32 AF XY: 0.0000191 AC XY: 13AN XY: 680984
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74448
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CHARGE syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2023 | - - |
CHD7-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 24, 2022 | 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). - |
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