rs867230

Positions:

• chr8-27610986-C-A
• chr8-27610986-C-G
• chr8-27610986-C-T

Variant summary

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

The ENST00000316403.15(CLU):​c.-29-386G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 359,682 control chromosomes in the GnomAD database, including 70,504 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 0.63 (29976 hom., cov: 32)
  • Exomes 𝑓: 0.62 (40528 hom.)
• Consequence: CLU ENST00000316403.15 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.-29-386G>T		intron_variant		ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.226+160G>T		intron_variant, non_coding_transcript_variant
CLU	NR_045494.1	n.152-386G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.-29-386G>T		intron_variant		1	NM_001831.4	ENSP00000315130	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95188 AN: 151742 Hom.: 29955 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.627

GnomAD4 exome AF: 0.621 AC: 129074 AN: 207822 Hom.: 40528 Cov.: 0 AF XY: 0.628 AC XY: 71630 AN XY: 114122

Gnomad4 AFR exome AF: 0.655

Gnomad4 AMR exome AF: 0.655

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.606

GnomAD4 genome AF: 0.627 AC: 95264 AN: 151860 Hom.: 29976 Cov.: 32 AF XY: 0.630 AC XY: 46767 AN XY: 74198

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.630

Alfa AF: 0.609 Hom.: 5762

Bravo AF: 0.636

Asia WGS AF: 0.713 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.67
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs867230; hg19: chr8-27468503;