Variant rs9331939 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

CLU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.204 with no splicing effect.

BS1

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. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 924 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLU	NM_001831.4 linkuse as main transcript	c.984C>T	p.Asp328=	synonymous_variant	7/9	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2 linkuse as main transcript	n.1239C>T		non_coding_transcript_exon_variant	7/9
CLU	NR_045494.1 linkuse as main transcript	n.1164C>T		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 linkuse as main transcript	c.984C>T	p.Asp328=	synonymous_variant	7/9	1	NM_001831.4	ENSP00000315130	P1	P10909-1

Frequencies

GnomAD3 genomes

AF:

0.00607

AC:

924

AN:

152194

Hom.:

Cov.:

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.:

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.:

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

AF:

0.00607

AC:

924

AN:

152312

Hom.:

Cov.:

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.:

Bravo

AF:

0.00567

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00895

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over