chr17-8121673-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001165967.2(HES7):c.591C>T(p.Pro197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,327,368 control chromosomes in the GnomAD database, including 8 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: 𝑓 0.0033 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00094 ( 5 hom. )
Consequence
HES7
NM_001165967.2 synonymous
NM_001165967.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.781
Genes affected
HES7 (HGNC:15977): (hes family bHLH transcription factor 7) This gene encodes a member of the hairy and enhancer of split family of bHLH transcription factors. The mouse ortholog of this gene is regulated by Notch signaling. The protein functions as a transcriptional repressor, and is implicated in correct patterning of the axial skeleton. A mutation in this gene has been shown to result in spondylocostal dysostosis. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 17-8121673-G-A is Benign according to our data. Variant chr17-8121673-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 288808.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BP7
Synonymous conserved (PhyloP=0.781 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00329 (501/152190) while in subpopulation AFR AF= 0.00773 (321/41544). AF 95% confidence interval is 0.00703. There are 3 homozygotes in gnomad4. There are 242 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HES7 | NM_001165967.2 | c.591C>T | p.Pro197= | synonymous_variant | 4/4 | ENST00000541682.7 | |
HES7 | NM_032580.4 | c.576C>T | p.Pro192= | synonymous_variant | 4/4 | ||
HES7 | XM_047436940.1 | c.687C>T | p.Pro229= | synonymous_variant | 3/3 | ||
HES7 | XM_047436941.1 | c.678C>T | p.Pro226= | synonymous_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HES7 | ENST00000541682.7 | c.591C>T | p.Pro197= | synonymous_variant | 4/4 | 1 | NM_001165967.2 | A1 | |
HES7 | ENST00000317814.8 | c.576C>T | p.Pro192= | synonymous_variant | 4/4 | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00329 AC: 501AN: 152082Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000693 AC: 1AN: 1444Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 798
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GnomAD4 exome AF: 0.000939 AC: 1104AN: 1175178Hom.: 5 Cov.: 30 AF XY: 0.000910 AC XY: 514AN XY: 564664
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GnomAD4 genome AF: 0.00329 AC: 501AN: 152190Hom.: 3 Cov.: 32 AF XY: 0.00325 AC XY: 242AN XY: 74414
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 28, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
HES7-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2023 | 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). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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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