dbSNP rs9331888: CLU:c.-229G>C (chr8-27611345-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000405140.7(CLU):c.-229G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 456,164 control chromosomes in the GnomAD database, including 24,940 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 6681 hom., cov: 32)

Exomes 𝑓: 0.33 ( 18259 hom. )

Consequence

CLU
ENST00000405140.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.194

Publications

116 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CLU	NM_001831.4 link	c.-29-745G>C	intron_variant	Intron 1 of 8	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2 link	n.27G>C	non_coding_transcript_exon_variant	Exon 1 of 9
CLU	NR_045494.1 link	n.151+256G>C	intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 link	c.-29-745G>C		intron_variant	Intron 1 of 8	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42705

AN:

152020

Hom.:

6673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.279

GnomAD2 exomes

AF:

0.351

AC:

47344

AN:

135074

AF XY:

0.345

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.319

GnomAD4 exome

AF:

0.335

AC:

101762

AN:

304026

Hom.:

18259

Cov.:

AF XY:

0.337

AC XY:

58340

AN XY:

173176

show subpopulations

African (AFR)

AF:

0.168

AC:

1443

AN:

8600

American (AMR)

AF:

0.503

AC:

13751

AN:

27320

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

2776

AN:

10816

East Asian (EAS)

AF:

0.455

AC:

4273

AN:

9394

South Asian (SAS)

AF:

0.378

AC:

22586

AN:

59674

European-Finnish (FIN)

AF:

0.356

AC:

4589

AN:

12876

Middle Eastern (MID)

AF:

0.272

AC:

317

AN:

1166

European-Non Finnish (NFE)

AF:

0.298

AC:

47683

AN:

160038

Other (OTH)

AF:

0.307

AC:

4344

AN:

14142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

5495

10990

16484

21979

27474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

380

760

1140

1520

1900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.281

AC:

42730

AN:

152138

Hom.:

6681

Cov.:

AF XY:

0.289

AC XY:

21512

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.163

AC:

6750

AN:

41530

American (AMR)

AF:

0.403

AC:

6159

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

838

AN:

3470

East Asian (EAS)

AF:

0.465

AC:

2397

AN:

5152

South Asian (SAS)

AF:

0.404

AC:

1949

AN:

4824

European-Finnish (FIN)

AF:

0.365

AC:

3866

AN:

10584

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19918

AN:

67970

Other (OTH)

AF:

0.285

AC:

602

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1548

3097

4645

6194

7742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.292

Hom.:

1322

Bravo

AF:

0.277

Asia WGS

AF:

0.441

AC:

1532

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.5

(source)

DANN

Benign

0.64

PhyloP100

0.19

PromoterAI

0.093

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over