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GeneBe

rs9331937

chr8-27599990-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001831.4(CLU):c.954C>G(p.Pro318=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,614,098 control chromosomes in the GnomAD database, including 361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 183 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 178 hom. )

Consequence

CLU
NM_001831.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.66
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=-0.86).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-27599990-G-C is Benign according to our data. Variant chr8-27599990-G-C is described in ClinVar as [Benign]. Clinvar id is 776304.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=-3.66 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLUNM_001831.4 linkuse as main transcriptc.954C>G p.Pro318= synonymous_variant 7/9 ENST00000316403.15
CLUNR_038335.2 linkuse as main transcriptn.1209C>G non_coding_transcript_exon_variant 7/9
CLUNR_045494.1 linkuse as main transcriptn.1134C>G non_coding_transcript_exon_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLUENST00000316403.15 linkuse as main transcriptc.954C>G p.Pro318= synonymous_variant 7/91 NM_001831.4 P1P10909-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0259
AC:
3939
AN:
152164
Hom.:
182
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0902
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00909
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.0225
GnomAD3 exomes
AF:
0.00719
AC:
1808
AN:
251360
Hom.:
76
AF XY:
0.00518
AC XY:
704
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.0975
Gnomad AMR exome
AF:
0.00520
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.00391
GnomAD4 exome
AF:
0.00270
AC:
3950
AN:
1461816
Hom.:
178
Cov.:
31
AF XY:
0.00231
AC XY:
1681
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.0942
Gnomad4 AMR exome
AF:
0.00566
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000854
Gnomad4 OTH exome
AF:
0.00656
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0259
AC:
3950
AN:
152282
Hom.:
183
Cov.:
32
AF XY:
0.0251
AC XY:
1872
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0902
Gnomad4 AMR
AF:
0.00908
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.0223
Alfa
AF:
0.00747
Hom.:
15
Bravo
AF:
0.0302
Asia WGS
AF:
0.00318
AC:
11
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
0.10
Dann
Benign
0.49
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: rs9331937; hg19: chr8-27457507; API