8-60742611-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_017780.4(CHD7):c.1179A>G(p.Pro393Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,612,676 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_017780.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00159 AC: 241AN: 151826Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000346 AC: 86AN: 248752Hom.: 0 AF XY: 0.000296 AC XY: 40AN XY: 134928
GnomAD4 exome AF: 0.000157 AC: 229AN: 1460732Hom.: 1 Cov.: 32 AF XY: 0.000128 AC XY: 93AN XY: 726486
GnomAD4 genome AF: 0.00160 AC: 243AN: 151944Hom.: 0 Cov.: 32 AF XY: 0.00158 AC XY: 117AN XY: 74242
ClinVar
Submissions by phenotype
not specified Benign:3
p.Pro393Pro in exon 2 of CHD7: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.48% (47/9800) of Af rican chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs111238892). -
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not provided Benign:3
CHD7: BP4, BP7, BS1 -
Variant summary: The CHD7 c.1179A>G (p.Pro393Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 50/120332 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0047959 (47/9800). This frequency is about 110 times the estimated maximal expected allele frequency of a pathogenic CHD7 variant (0.0000438), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. This variant has been reported as a benign variant in one CHARGE syndrome patient (Janssen_HM_2012). Taken together, this variant is classified as benign. -
This variant is associated with the following publications: (PMID: 22461308) -
CHARGE syndrome Benign:1
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
CHARGE syndrome;C3552553:Hypogonadotropic hypogonadism 5 with or without anosmia Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at