rs1060503183
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_017780.4(CHD7):c.3202-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_017780.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.3202-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.3202-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_017780.4 | P1 | |||
CHD7 | ENST00000524602.5 | c.1717-38392T>C | intron_variant | 1 | |||||
CHD7 | ENST00000525508.1 | c.3202-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
CHD7 | ENST00000695853.1 | c.3202-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248132Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134756
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460186Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726460
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
CHARGE syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change falls in intron 12 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 (no rsID available, gnomAD 0.01%). 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: 1022057). 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. This variant disrupts the c.3202-3T nucleotide in the CHD7 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 22033296; Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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 | Apr 28, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at