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GeneBe

8-27608992-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001831.4(CLU):c.192C>T(p.Asn64=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00053 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00054 ( 1 hom. )

Consequence

CLU
NM_001831.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.45
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-27608992-G-A is Benign according to our data. Variant chr8-27608992-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.45 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 60 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLUNM_001831.4 linkuse as main transcriptc.192C>T p.Asn64= synonymous_variant 3/9 ENST00000316403.15
CLUNR_038335.2 linkuse as main transcriptn.447C>T non_coding_transcript_exon_variant 3/9
CLUNR_045494.1 linkuse as main transcriptn.372C>T non_coding_transcript_exon_variant 3/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLUENST00000316403.15 linkuse as main transcriptc.192C>T p.Asn64= synonymous_variant 3/91 NM_001831.4 P1P10909-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000394
AC:
60
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000485
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000473
AC:
119
AN:
251480
Hom.:
0
AF XY:
0.000441
AC XY:
60
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.00124
Gnomad ASJ exome
AF:
0.00218
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000325
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.000544
AC:
795
AN:
1461846
Hom.:
1
Cov.:
32
AF XY:
0.000479
AC XY:
348
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.00125
Gnomad4 ASJ exome
AF:
0.00256
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000559
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000394
AC:
60
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.000430
AC XY:
32
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000485
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000393
Hom.:
0
Bravo
AF:
0.000495
EpiCase
AF:
0.000382
EpiControl
AF:
0.000296

ClinVar

Significance: 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 submitterclinical testingPreventionGenetics, part of Exact SciencesOct 28, 2019This 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
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023CLU: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
0.18
Dann
Benign
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146277764; hg19: chr8-27466509; API