chr8-27605145-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 15/22 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, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.91

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 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_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 325 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4 link	c.608C>T	p.Thr203Ile	missense_variant	Exon 5 of 9	ENST00000316403.15	NP_001822.3	P10909-1
CLU	NR_038335.2 link	n.863C>T		non_coding_transcript_exon_variant	Exon 5 of 9
CLU	NR_045494.1 link	n.788C>T		non_coding_transcript_exon_variant	Exon 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 link	c.608C>T	p.Thr203Ile	missense_variant	Exon 5 of 9	1	NM_001831.4	ENSP00000315130.10		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

GnomAD2 exomes

AF:

0.00196

AC:

493

AN:

251434

AF XY:

0.00200

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 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

African (AFR)

AF:

0.000538

AC:

AN:

33480

American (AMR)

AF:

0.00145

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000749

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00463

AC:

5152

AN:

1112008

Other (OTH)

AF:

0.00381

AC:

230

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

330

660

991

1321

1651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00213

AC:

325

AN:

152314

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

147

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41568

American (AMR)

AF:

0.00242

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00365

AC:

248

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00251

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CLU: BP4, BS2 -

Alzheimer disease

Benign:1

Myllykangas group, University of Helsinki

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:research

- -

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

(source)

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

LIST_S2

Benign

0.52

.;.;T;T;T

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;.;.

PhyloP100

1.9

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

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.35

Mutation Taster

=100/0

polymorphism

(source)

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

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chr8-27605145-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over