rs760775347
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_017780.4(CHD7):āc.839C>Gā(p.Pro280Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,832 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P280S) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.839C>G | p.Pro280Arg | missense_variant | 2/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.839C>G | p.Pro280Arg | missense_variant | 2/38 | 5 | NM_017780.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248868Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135082
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461682Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727128
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2023 | The p.P280R variant (also known as c.839C>G), located in coding exon 1 of the CHD7 gene, results from a C to G substitution at nucleotide position 839. The proline at codon 280 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 16, 2023 | 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 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
CHARGE syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at