Variant 8-27605145-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001831.4(CLU):c.608C>T(p.Thr203Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,614,200 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

CLU
NM_001831.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.91

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072170794).

BP6

Variant 8-27605145-G-A is Benign according to our data. Variant chr8-27605145-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 428612.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 325 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLU	NM_001831.4 linkuse as main transcript	c.608C>T	p.Thr203Ile	missense_variant	5/9	ENST00000316403.15
CLU	NR_038335.2 linkuse as main transcript	n.863C>T		non_coding_transcript_exon_variant	5/9
CLU	NR_045494.1 linkuse as main transcript	n.788C>T		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLU	ENST00000316403.15 linkuse as main transcript	c.608C>T	p.Thr203Ile	missense_variant	5/9	1	NM_001831.4	P1	P10909-1

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

325

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00365

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00196

AC:

493

AN:

251434

Hom.:

AF XY:

0.00200

AC XY:

272

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00377

AC:

5514

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

2657

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.00463

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00213

AC:

325

AN:

152314

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

147

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00365

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00292

Hom.:

Bravo

AF:

0.00218

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00167

AC:

203

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00326

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 10, 2018

- -

Alzheimer disease

Benign:1

Likely benign, no assertion criteria provided

research

Myllykangas group, University of Helsinki

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

Cadd

Benign

8.1

Dann

Benign

0.71

DEOGEN2

Benign

0.12

T;T;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

M_CAP

Benign

0.0072

MetaRNN

Benign

0.0072

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M;M;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.066

Sift

Benign

0.40

T;T;T;T;T

Sift4G

Benign

0.16

T;T;T;.;D

Polyphen

0.0060

B;B;B;.;.

Vest4

0.080

MVP

0.36

MPC

0.53

ClinPred

0.0071

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.35

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.

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