rs9331888

Positions:

• chr8-27611345-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000405140.7(CLU):​c.-229G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 456,164 control chromosomes in the GnomAD database, including 24,940 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 0.28 (6681 hom., cov: 32)
  • Exomes 𝑓: 0.33 (18259 hom.)
• Consequence: CLU ENST00000405140.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.-29-745G>C		intron_variant		ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.27G>C		non_coding_transcript_exon_variant	1/9
CLU	NR_045494.1	n.151+256G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.-29-745G>C		intron_variant		1	NM_001831.4	ENSP00000315130	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42705 AN: 152020 Hom.: 6673 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.279

GnomAD3 exomes AF: 0.351 AC: 47344 AN: 135074 Hom.: 9093 AF XY: 0.345 AC XY: 25384 AN XY: 73490

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.467

Gnomad SAS exome AF: 0.382

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.319

GnomAD4 exome AF: 0.335 AC: 101762 AN: 304026 Hom.: 18259 Cov.: 0 AF XY: 0.337 AC XY: 58340 AN XY: 173176

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.281 AC: 42730 AN: 152138 Hom.: 6681 Cov.: 32 AF XY: 0.289 AC XY: 21512 AN XY: 74388

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.285

Alfa AF: 0.292 Hom.: 1322

Bravo AF: 0.277

Asia WGS AF: 0.441 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.64

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: rs9331888; hg19: chr8-27468862;