17-8121685-G-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_001165967.2(HES7):c.579C>A(p.Gly193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000761 in 1,326,652 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000082 ( 0 hom. )
Consequence
HES7
NM_001165967.2 synonymous
NM_001165967.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.874
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 -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 17-8121685-G-T is Benign according to our data. Variant chr17-8121685-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1532977.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.874 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000817 (96/1174528) while in subpopulation SAS AF= 0.00185 (80/43324). AF 95% confidence interval is 0.00152. There are 0 homozygotes in gnomad4_exome. There are 64 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HES7 | NM_001165967.2 | c.579C>A | p.Gly193= | synonymous_variant | 4/4 | ENST00000541682.7 | |
HES7 | NM_032580.4 | c.564C>A | p.Gly188= | synonymous_variant | 4/4 | ||
HES7 | XM_047436940.1 | c.675C>A | p.Gly225= | synonymous_variant | 3/3 | ||
HES7 | XM_047436941.1 | c.666C>A | p.Gly222= | synonymous_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HES7 | ENST00000541682.7 | c.579C>A | p.Gly193= | synonymous_variant | 4/4 | 1 | NM_001165967.2 | A1 | |
HES7 | ENST00000317814.8 | c.564C>A | p.Gly188= | synonymous_variant | 4/4 | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152124Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000397 AC: 1AN: 2522Hom.: 0 AF XY: 0.000658 AC XY: 1AN XY: 1520
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GnomAD4 exome AF: 0.0000817 AC: 96AN: 1174528Hom.: 0 Cov.: 30 AF XY: 0.000113 AC XY: 64AN XY: 564358
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74320
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 22, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at