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GeneBe

8-27604964-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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.467
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 -15 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=-0.95).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-27604964-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
?
    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=-0.467 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
CLUNM_001831.4 linkuse as main transcriptc.789T>C p.His263= synonymous_variant 5/9 ENST00000316403.15
CLUNR_038335.2 linkuse as main transcriptn.1044T>C non_coding_transcript_exon_variant 5/9
CLUNR_045494.1 linkuse as main transcriptn.969T>C non_coding_transcript_exon_variant 5/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLUENST00000316403.15 linkuse as main transcriptc.789T>C p.His263= synonymous_variant 5/91 NM_001831.4 P1P10909-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.608
AC:
92335
AN:
151818
Hom.:
28209
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.571
Gnomad AMI
AF:
0.631
Gnomad AMR
AF:
0.649
Gnomad ASJ
AF:
0.590
Gnomad EAS
AF:
0.788
Gnomad SAS
AF:
0.705
Gnomad FIN
AF:
0.597
Gnomad MID
AF:
0.623
Gnomad NFE
AF:
0.603
Gnomad OTH
AF:
0.616
GnomAD3 exomes
AF:
0.636
AC:
160034
AN:
251456
Hom.:
51304
AF XY:
0.638
AC XY:
86746
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.573
Gnomad AMR exome
AF:
0.677
Gnomad ASJ exome
AF:
0.600
Gnomad EAS exome
AF:
0.782
Gnomad SAS exome
AF:
0.700
Gnomad FIN exome
AF:
0.600
Gnomad NFE exome
AF:
0.603
Gnomad OTH exome
AF:
0.630
GnomAD4 exome
AF:
0.611
AC:
893139
AN:
1461818
Hom.:
274300
Cov.:
63
AF XY:
0.614
AC XY:
446328
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.569
Gnomad4 AMR exome
AF:
0.670
Gnomad4 ASJ exome
AF:
0.598
Gnomad4 EAS exome
AF:
0.763
Gnomad4 SAS exome
AF:
0.695
Gnomad4 FIN exome
AF:
0.594
Gnomad4 NFE exome
AF:
0.599
Gnomad4 OTH exome
AF:
0.618
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.608
AC:
92411
AN:
151936
Hom.:
28231
Cov.:
31
AF XY:
0.612
AC XY:
45465
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.571
Gnomad4 AMR
AF:
0.649
Gnomad4 ASJ
AF:
0.590
Gnomad4 EAS
AF:
0.788
Gnomad4 SAS
AF:
0.705
Gnomad4 FIN
AF:
0.597
Gnomad4 NFE
AF:
0.603
Gnomad4 OTH
AF:
0.618
Alfa
AF:
0.608
Hom.:
22633
Bravo
AF:
0.612
Asia WGS
AF:
0.726
AC:
2523
AN:
3478
EpiCase
AF:
0.613
EpiControl
AF:
0.606

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 submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
Cadd
Benign
0.39
Dann
Benign
0.39
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: rs7982; hg19: chr8-27462481; COSMIC: COSV57065941; COSMIC: COSV57065941; API