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

Variant summary

Our verdict is Benign. Variant got -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

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:

LOC124901919 (HGNC:):

LOC124901919 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.*644T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_001831.4	ENSP00000315130.10		P10909-1
CLU	ENST00000405140.7 link	c.*644T>C		downstream_gene_variant		1		ENSP00000385419.3		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

GnomAD3 exomes

AF:

0.0740

AC:

9699

AN:

131036

Hom.:

872

AF XY:

0.0807

AC XY:

5770

AN XY:

71526

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 SAS exome

AF:

0.148

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

Gnomad4 AFR exome

AF:

0.0883

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.0274

Gnomad4 EAS exome

AF:

0.316

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.0828

Gnomad4 NFE exome

AF:

0.0297

Gnomad4 OTH exome

AF:

0.0530

GnomAD4 genome

AF:

0.0595

AC:

9060

AN:

152302

Hom.:

546

Cov.:

AF XY:

0.0642

AC XY:

4779

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0800

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.0925

Gnomad4 NFE

AF:

0.0276

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0418

Hom.:

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

DANN

Benign

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over