Genetic Variant CLU:c.1165-101A>G (chr8-27598736-T-C) – 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.1165-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,137,980 control chromosomes in the GnomAD database, including 225,366 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 0.69 ( 37777 hom., cov: 32)

Exomes 𝑓: 0.61 ( 187589 hom. )

Consequence

CLU
NM_001831.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.327

Publications

114 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:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLU	NM_001831.4	MANE Select	c.1165-101A>G	intron	N/A	NP_001822.3
CLU	NR_038335.2		n.1420-101A>G	intron	N/A
CLU	NR_045494.1		n.1345-101A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLU	ENST00000316403.15	TSL:1 MANE Select	c.1165-101A>G	intron	N/A	ENSP00000315130.10
CLU	ENST00000405140.7	TSL:1	c.1165-101A>G	intron	N/A	ENSP00000385419.3
CLU	ENST00000523500.5	TSL:1	c.1165-101A>G	intron	N/A	ENSP00000429620.1

Frequencies

GnomAD3 genomes

AF:

0.692

AC:

105244

AN:

152024

Hom.:

37723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.895

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.589

Gnomad OTH

AF:

0.673

GnomAD4 exome

AF:

0.612

AC:

602855

AN:

985838

Hom.:

187589

Cov.:

AF XY:

0.613

AC XY:

312972

AN XY:

510212

show subpopulations

African (AFR)

AF:

0.898

AC:

21578

AN:

24036

American (AMR)

AF:

0.676

AC:

28290

AN:

41878

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

14194

AN:

23078

East Asian (EAS)

AF:

0.762

AC:

28210

AN:

37018

South Asian (SAS)

AF:

0.692

AC:

52135

AN:

75340

European-Finnish (FIN)

AF:

0.583

AC:

23899

AN:

41000

Middle Eastern (MID)

AF:

0.609

AC:

2750

AN:

4516

European-Non Finnish (NFE)

AF:

0.581

AC:

403487

AN:

693944

Other (OTH)

AF:

0.629

AC:

28312

AN:

45028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

12909

25818

38727

51636

64545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8756

17512

26268

35024

43780

<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:

0.692

AC:

105358

AN:

152142

Hom.:

37777

Cov.:

AF XY:

0.693

AC XY:

51496

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.895

AC:

37155

AN:

41526

American (AMR)

AF:

0.673

AC:

10289

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2108

AN:

3470

East Asian (EAS)

AF:

0.786

AC:

4063

AN:

5170

South Asian (SAS)

AF:

0.702

AC:

3389

AN:

4826

European-Finnish (FIN)

AF:

0.584

AC:

6171

AN:

10570

Middle Eastern (MID)

AF:

0.603

AC:

176

AN:

292

European-Non Finnish (NFE)

AF:

0.588

AC:

40001

AN:

67976

Other (OTH)

AF:

0.675

AC:

1425

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1557

3114

4670

6227

7784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.629

Hom.:

95508

Bravo

AF:

0.710

Asia WGS

AF:

0.745

AC:

2588

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.8

(source)

DANN

Benign

0.36

PhyloP100

-0.33

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over