chr8-27604964-A-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_001831.4(CLU):c.789T>C(p.His263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,613,754 control chromosomes in the GnomAD database, including 302,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.61 ( 28231 hom., cov: 31)
Exomes 𝑓: 0.61 ( 274300 hom. )
Consequence
CLU
NM_001831.4 synonymous
NM_001831.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.467
Genes affected
CLU (HGNC:2095): (clusterin) The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Alternate splicing results in both coding and non-coding variants.[provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
?
Variant 8-27604964-A-G is Benign according to our data. Variant chr8-27604964-A-G is described in ClinVar as [Benign]. Clinvar id is 3060904.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.467 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLU | NM_001831.4 | c.789T>C | p.His263= | synonymous_variant | 5/9 | ENST00000316403.15 | |
CLU | NR_038335.2 | n.1044T>C | non_coding_transcript_exon_variant | 5/9 | |||
CLU | NR_045494.1 | n.969T>C | non_coding_transcript_exon_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLU | ENST00000316403.15 | c.789T>C | p.His263= | synonymous_variant | 5/9 | 1 | NM_001831.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.608 AC: 92335AN: 151818Hom.: 28209 Cov.: 31
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GnomAD3 exomes AF: 0.636 AC: 160034AN: 251456Hom.: 51304 AF XY: 0.638 AC XY: 86746AN XY: 135904
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GnomAD4 exome AF: 0.611 AC: 893139AN: 1461818Hom.: 274300 Cov.: 63 AF XY: 0.614 AC XY: 446328AN XY: 727214
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GnomAD4 genome ? AF: 0.608 AC: 92411AN: 151936Hom.: 28231 Cov.: 31 AF XY: 0.612 AC XY: 45465AN XY: 74254
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CLU-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as 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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Name
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BayesDel_noAF
Benign
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RBP_binding_hub_radar
RBP_regulation_power_radar
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