Genetic Variant CLU:c.246+274A>C (chr8-27608664-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001831.4(CLU):c.246+274A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000725 in 413,570 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

CLU
NM_001831.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.765

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CLU	NM_001831.4 link	c.246+274A>C	intron_variant	Intron 3 of 8	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2 link	n.501+274A>C	intron_variant	Intron 3 of 8
CLU	NR_045494.1 link	n.426+274A>C	intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 link	c.246+274A>C		intron_variant	Intron 3 of 8	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000725

AC:

AN:

413570

Hom.:

Cov.:

AF XY:

0.00000916

AC XY:

AN XY:

218394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11632

American (AMR)

AF:

0.00

AC:

AN:

17386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12530

East Asian (EAS)

AF:

0.00

AC:

AN:

27840

South Asian (SAS)

AF:

0.0000679

AC:

AN:

44214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1818

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

247658

Other (OTH)

AF:

0.00

AC:

AN:

23746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.5

(source)

DANN

Benign

0.45

PhyloP100

-0.77

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over