Menu
GeneBe

rs9331939

chr8-27599960-G-Achr8-27599960-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001831.4(CLU):c.984C>T(p.Asp328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00971 in 1,614,184 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 4 hom., cov: 32)
Exomes 𝑓: 0.010 ( 108 hom. )

Consequence

CLU
NM_001831.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.204
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=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-27599960-G-A is Benign according to our data. Variant chr8-27599960-G-A is described in ClinVar as [Benign]. Clinvar id is 788866.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=0.204 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00607 (924/152312) while in subpopulation SAS AF= 0.0228 (110/4826). AF 95% confidence interval is 0.0193. There are 4 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. This position pass quality control queck.
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 924 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLUNM_001831.4 linkuse as main transcriptc.984C>T p.Asp328= synonymous_variant 7/9 ENST00000316403.15
CLUNR_038335.2 linkuse as main transcriptn.1239C>T non_coding_transcript_exon_variant 7/9
CLUNR_045494.1 linkuse as main transcriptn.1164C>T 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.984C>T p.Asp328= synonymous_variant 7/91 NM_001831.4 P1P10909-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00607
AC:
924
AN:
152194
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00174
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00380
Gnomad ASJ
AF:
0.0323
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0228
Gnomad FIN
AF:
0.00377
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00766
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00901
AC:
2264
AN:
251386
Hom.:
21
AF XY:
0.00998
AC XY:
1356
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00154
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.0328
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0217
Gnomad FIN exome
AF:
0.00319
Gnomad NFE exome
AF:
0.00908
Gnomad OTH exome
AF:
0.00978
GnomAD4 exome
AF:
0.0101
AC:
14748
AN:
1461872
Hom.:
108
Cov.:
31
AF XY:
0.0105
AC XY:
7604
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00164
Gnomad4 AMR exome
AF:
0.00257
Gnomad4 ASJ exome
AF:
0.0339
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0224
Gnomad4 FIN exome
AF:
0.00401
Gnomad4 NFE exome
AF:
0.00977
Gnomad4 OTH exome
AF:
0.0102
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00607
AC:
924
AN:
152312
Hom.:
4
Cov.:
32
AF XY:
0.00616
AC XY:
459
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00173
Gnomad4 AMR
AF:
0.00379
Gnomad4 ASJ
AF:
0.0323
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0228
Gnomad4 FIN
AF:
0.00377
Gnomad4 NFE
AF:
0.00766
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00948
Hom.:
13
Bravo
AF:
0.00567
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.00905
EpiControl
AF:
0.00895

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
-0.81
Cadd
Benign
3.5
Dann
Benign
0.36
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs9331939; hg19: chr8-27457477; API