8-60841997-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_017780.4(CHD7):c.4795C>G(p.Gln1599Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1599R) has been classified as Uncertain significance.
Frequency
Consequence
NM_017780.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.4795C>G | p.Gln1599Glu | missense_variant | 21/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.4795C>G | p.Gln1599Glu | missense_variant | 21/38 | 5 | NM_017780.4 | P1 | |
CHD7 | ENST00000524602.5 | c.1717-20232C>G | intron_variant | 1 | |||||
CHD7 | ENST00000695853.1 | c.4795C>G | p.Gln1599Glu | missense_variant, NMD_transcript_variant | 21/37 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248200Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134678
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461644Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727096
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
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 16, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
CHARGE syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at