rs762730711
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_017780.4(CHD7):c.6936+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000272 in 1,581,614 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 Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
CHD7
NM_017780.4 splice_donor_region, intron
NM_017780.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001788
2
Clinical Significance
Conservation
PhyloP100: 0.195
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BS2
High AC in GnomAdExome4 at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.6936+6C>T | splice_donor_region_variant, intron_variant | ENST00000423902.7 | NP_060250.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.6936+6C>T | splice_donor_region_variant, intron_variant | 5 | NM_017780.4 | ENSP00000392028 | P1 | |||
CHD7 | ENST00000524602.5 | c.1717-7700C>T | intron_variant | 1 | ENSP00000437061 | |||||
CHD7 | ENST00000695853.1 | c.6775+1029C>T | intron_variant, NMD_transcript_variant | ENSP00000512218 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000210 AC: 5AN: 237678Hom.: 0 AF XY: 0.0000233 AC XY: 3AN XY: 128664
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GnomAD4 exome AF: 0.0000287 AC: 41AN: 1429438Hom.: 0 Cov.: 31 AF XY: 0.0000227 AC XY: 16AN XY: 705842
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CHARGE syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 04, 2024 | This sequence change falls in intron 32 of the CHD7 gene. It does not directly change the encoded amino acid sequence of the CHD7 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs762730711, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with CHD7-related conditions. ClinVar contains an entry for this variant (Variation ID: 529130). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
CHARGE syndrome;C3552553:Hypogonadotropic hypogonadism 5 with or without anosmia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 03, 2022 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at