Genetic Variant CLU:c.*1183G>A (chr8-27597058-C-T) – 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.*1183G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 454,004 control chromosomes in the GnomAD database, including 791 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 0.066 ( 522 hom., cov: 32)

Exomes 𝑓: 0.035 ( 269 hom. )

Consequence

CLU
NM_001831.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.196

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=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4 link	c.*1183G>A	3_prime_UTR_variant	Exon 9 of 9	ENST00000316403.15	NP_001822.3	P10909-1
CLU	NR_038335.2 link	n.2788G>A	non_coding_transcript_exon_variant	Exon 9 of 9
CLU	NR_045494.1 link	n.2713G>A	non_coding_transcript_exon_variant	Exon 9 of 9
LOC124901919	XR_007060868.1 link	n.1398-9C>T	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 link	c.*1183G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001831.4	ENSP00000315130.10		P10909-1

Frequencies

GnomAD3 genomes

AF:

0.0655

AC:

9968

AN:

152094

Hom.:

522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0474

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0411

Gnomad OTH

AF:

0.0603

GnomAD2 exomes

AF:

0.0354

AC:

4622

AN:

130548

AF XY:

0.0332

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0320

Gnomad ASJ exome

AF:

0.0257

Gnomad EAS exome

AF:

0.00949

Gnomad FIN exome

AF:

0.0210

Gnomad NFE exome

AF:

0.0424

Gnomad OTH exome

AF:

0.0367

GnomAD4 exome

AF:

0.0349

AC:

10544

AN:

301792

Hom.:

269

Cov.:

AF XY:

0.0324

AC XY:

5575

AN XY:

171994

show subpopulations

African (AFR)

AF:

0.137

AC:

1175

AN:

8552

American (AMR)

AF:

0.0322

AC:

879

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

273

AN:

10786

East Asian (EAS)

AF:

0.00988

AC:

AN:

9210

South Asian (SAS)

AF:

0.0156

AC:

930

AN:

59650

European-Finnish (FIN)

AF:

0.0202

AC:

250

AN:

12364

Middle Eastern (MID)

AF:

0.0174

AC:

AN:

1150

European-Non Finnish (NFE)

AF:

0.0401

AC:

6371

AN:

158764

Other (OTH)

AF:

0.0395

AC:

555

AN:

14042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

824

1648

2471

3295

4119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0656

AC:

9982

AN:

152212

Hom.:

522

Cov.:

AF XY:

0.0630

AC XY:

4691

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.142

AC:

5905

AN:

41500

American (AMR)

AF:

0.0474

AC:

725

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

AN:

3472

East Asian (EAS)

AF:

0.0116

AC:

AN:

5182

South Asian (SAS)

AF:

0.0139

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0175

AC:

186

AN:

10610

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0411

AC:

2792

AN:

68014

Other (OTH)

AF:

0.0597

AC:

126

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

466

933

1399

1866

2332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0480

Hom.:

1010

Bravo

AF:

0.0713

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.5

(source)

DANN

Benign

0.66

PhyloP100

0.20

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