dbSNP rs9331942: CLU:c.*644T>C (chr8-27597597-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001831.4(CLU):c.*644T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 454,096 control chromosomes in the GnomAD database, including 1,944 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 0.059 ( 546 hom., cov: 32)

Exomes 𝑓: 0.065 ( 1398 hom. )

Consequence

CLU
NM_001831.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

10 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:

ENSG00000300853 (HGNC:):

ENSG00000300853 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4 link	c.*644T>C	3_prime_UTR_variant	Exon 9 of 9	ENST00000316403.15	NP_001822.3	P10909-1
CLU	NR_038335.2 link	n.2249T>C	non_coding_transcript_exon_variant	Exon 9 of 9
CLU	NR_045494.1 link	n.2174T>C	non_coding_transcript_exon_variant	Exon 9 of 9
LOC124901919	XR_007060868.1 link	n.*38A>G	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 link	c.*644T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_001831.4	ENSP00000315130.10		P10909-1

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9060

AN:

152184

Hom.:

547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0801

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0925

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0276

Gnomad OTH

AF:

0.0468

GnomAD2 exomes

AF:

0.0740

AC:

9699

AN:

131036

AF XY:

0.0807

show subpopulations

Gnomad AFR exome

AF:

0.0887

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.0252

Gnomad EAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.0873

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0427

GnomAD4 exome

AF:

0.0649

AC:

19574

AN:

301794

Hom.:

1398

Cov.:

AF XY:

0.0737

AC XY:

12674

AN XY:

171996

show subpopulations

African (AFR)

AF:

0.0883

AC:

755

AN:

8554

American (AMR)

AF:

0.0117

AC:

318

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

295

AN:

10786

East Asian (EAS)

AF:

0.316

AC:

2907

AN:

9210

South Asian (SAS)

AF:

0.147

AC:

8779

AN:

59650

European-Finnish (FIN)

AF:

0.0828

AC:

1024

AN:

12364

Middle Eastern (MID)

AF:

0.0278

AC:

AN:

1150

European-Non Finnish (NFE)

AF:

0.0297

AC:

4720

AN:

158764

Other (OTH)

AF:

0.0530

AC:

744

AN:

14042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1366

2731

4097

5462

6828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.0595

AC:

9060

AN:

152302

Hom.:

546

Cov.:

AF XY:

0.0642

AC XY:

4779

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0800

AC:

3324

AN:

41546

American (AMR)

AF:

0.0176

AC:

269

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

AN:

3472

East Asian (EAS)

AF:

0.306

AC:

1584

AN:

5182

South Asian (SAS)

AF:

0.146

AC:

706

AN:

4822

European-Finnish (FIN)

AF:

0.0925

AC:

982

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0276

AC:

1879

AN:

68032

Other (OTH)

AF:

0.0454

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

419

839

1258

1678

2097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0457

Hom.:

600

Bravo

AF:

0.0556

Asia WGS

AF:

0.191

AC:

664

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.32

(source)

DANN

Benign

0.52

PhyloP100

-1.4

Mutation Taster

=100/0

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