rs61753399
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017780.4(CHD7):c.6478G>A(p.Ala2160Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 1,613,856 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_017780.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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CHD7 | ENST00000423902.7 | c.6478G>A | p.Ala2160Thr | missense_variant | Exon 31 of 38 | 5 | NM_017780.4 | ENSP00000392028.1 | ||
CHD7 | ENST00000524602.5 | c.1717-9026G>A | intron_variant | Intron 2 of 4 | 1 | ENSP00000437061.1 | ||||
CHD7 | ENST00000695853.1 | n.6478G>A | non_coding_transcript_exon_variant | Exon 31 of 37 | ENSP00000512218.1 |
Frequencies
GnomAD3 genomes AF: 0.00442 AC: 672AN: 152130Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00105 AC: 262AN: 248656Hom.: 1 AF XY: 0.000689 AC XY: 93AN XY: 134940
GnomAD4 exome AF: 0.000393 AC: 575AN: 1461608Hom.: 4 Cov.: 32 AF XY: 0.000319 AC XY: 232AN XY: 727084
GnomAD4 genome AF: 0.00441 AC: 671AN: 152248Hom.: 6 Cov.: 32 AF XY: 0.00398 AC XY: 296AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:8
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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p.Ala2160Thr in exon 31 of CHD7: This variant is not expected to have clinical significance because it has been identified in 1.47% (140/9514) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs61753399). -
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CHARGE syndrome Benign:2
This variant is interpreted as a Likely Benign, for CHARGE syndrome, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). -
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Inborn genetic diseases Benign:1
This alteration is classified as 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. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at