8-27610488-G-A

Position:

• chr8-27610488-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001831.4(CLU):​c.84C>T​(p.Asp28Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,613,914 control chromosomes in the GnomAD database, including 1,541 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 0.055 (828 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (713 hom.)
• Consequence: CLU NM_001831.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.907

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.907 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.84C>T	p.Asp28Asp	synonymous_variant	2/9	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.339C>T		non_coding_transcript_exon_variant	2/9
CLU	NR_045494.1	n.264C>T		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.84C>T	p.Asp28Asp	synonymous_variant	2/9	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8393 AN: 152208 Hom.: 828 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0406

GnomAD3 exomes AF: 0.0140 AC: 3528 AN: 251438 Hom.: 297 AF XY: 0.0102 AC XY: 1389 AN XY: 135894

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.00882

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00560 AC: 8184 AN: 1461588 Hom.: 713 Cov.: 31 AF XY: 0.00476 AC XY: 3460 AN XY: 727106

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.00964

Gnomad4 ASJ exome AF: 0.00264

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000291

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0552 AC: 8408 AN: 152326 Hom.: 828 Cov.: 33 AF XY: 0.0526 AC XY: 3915 AN XY: 74498

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0277 Hom.: 156

Bravo AF: 0.0628

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs9331892; hg19: chr8-27468005;