rs199828744
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_017780.4(CHD7):āc.6216C>Gā(p.Pro2072=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000764 in 1,613,950 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00037 ( 1 hom., cov: 32)
Exomes š: 0.00081 ( 2 hom. )
Consequence
CHD7
NM_017780.4 synonymous
NM_017780.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.83
Genes affected
CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 8-60852941-C-G is Benign according to our data. Variant chr8-60852941-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 95801.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Likely_benign=3, Uncertain_significance=1}. Variant chr8-60852941-C-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.83 with no splicing effect.
BS2
?
High AC in GnomAd4 at 56 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.6216C>G | p.Pro2072= | synonymous_variant | 31/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.6216C>G | p.Pro2072= | synonymous_variant | 31/38 | 5 | NM_017780.4 | P1 | |
CHD7 | ENST00000524602.5 | c.1717-9288C>G | intron_variant | 1 | |||||
CHD7 | ENST00000695853.1 | c.6216C>G | p.Pro2072= | synonymous_variant, NMD_transcript_variant | 31/37 |
Frequencies
GnomAD3 genomes ? AF: 0.000368 AC: 56AN: 152122Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000369 AC: 92AN: 249212Hom.: 0 AF XY: 0.000385 AC XY: 52AN XY: 135194
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GnomAD4 exome AF: 0.000805 AC: 1177AN: 1461710Hom.: 2 Cov.: 32 AF XY: 0.000794 AC XY: 577AN XY: 727138
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:7
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | CHD7: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 28, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 22, 2019 | This variant is associated with the following publications: (PMID: 23757202, 23885230, 30733481) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 10, 2023 | - - |
CHARGE syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 16, 2018 | 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. - |
CHD7-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 08, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hypogonadotropic hypogonadism 5 with or without anosmia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at