chr8-27606389-C-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001831.4(CLU):c.382G>A(p.Val128Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,614,242 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 1 hom. )
Consequence
CLU
NM_001831.4 missense
NM_001831.4 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: 3.14
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013203472).
BP6
?
Variant 8-27606389-C-T is Benign according to our data. Variant chr8-27606389-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 726773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 400 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLU | NM_001831.4 | c.382G>A | p.Val128Ile | missense_variant | 4/9 | ENST00000316403.15 | |
CLU | NR_038335.2 | n.637G>A | non_coding_transcript_exon_variant | 4/9 | |||
CLU | NR_045494.1 | n.562G>A | non_coding_transcript_exon_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLU | ENST00000316403.15 | c.382G>A | p.Val128Ile | missense_variant | 4/9 | 1 | NM_001831.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00263 AC: 400AN: 152244Hom.: 1 Cov.: 33
GnomAD3 genomes
?
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152244
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33
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GnomAD3 exomes AF: 0.000645 AC: 162AN: 251330Hom.: 1 AF XY: 0.000420 AC XY: 57AN XY: 135866
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GnomAD4 exome AF: 0.000291 AC: 425AN: 1461880Hom.: 1 Cov.: 32 AF XY: 0.000254 AC XY: 185AN XY: 727244
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GnomAD4 genome ? AF: 0.00263 AC: 401AN: 152362Hom.: 1 Cov.: 33 AF XY: 0.00256 AC XY: 191AN XY: 74500
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CLU-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 11, 2020 | 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T;T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.;.;.;.;.
MutationTaster
Benign
D;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;.;T;T;.;.
Polyphen
D;D;D;.;.;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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