rs9331931

Positions:

• chr8-27600587-G-C

Variant summary

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

The NM_001831.4(CLU):​c.935-578C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,076 control chromosomes in the GnomAD database, including 3,772 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 0.21 (3772 hom., cov: 32)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.935-578C>G		intron_variant		ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.1190-578C>G		intron_variant
CLU	NR_045494.1	n.1115-578C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.935-578C>G		intron_variant		1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32435 AN: 151958 Hom.: 3768 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.213 AC: 32456 AN: 152076 Hom.: 3772 Cov.: 32 AF XY: 0.206 AC XY: 15342 AN XY: 74334

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.233

Alfa AF: 0.230 Hom.: 535

Bravo AF: 0.216

Asia WGS AF: 0.0760 AC: 265 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	6.7
DANN	Benign	0.61

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: rs9331931; hg19: chr8-27458104;