rs9331908

Positions:

• chr8-27606101-C-T

Variant summary

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

The NM_001831.4(CLU):​c.417+253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,980 control chromosomes in the GnomAD database, including 10,565 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 0.36 (10565 hom., cov: 32)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.417+253G>A		intron_variant		ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.672+253G>A		intron_variant
CLU	NR_045494.1	n.597+253G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.417+253G>A		intron_variant		1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54073 AN: 151862 Hom.: 10563 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.356 AC: 54106 AN: 151980 Hom.: 10565 Cov.: 32 AF XY: 0.368 AC XY: 27329 AN XY: 74298

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.355

Alfa AF: 0.357 Hom.: 1822

Bravo AF: 0.352

Asia WGS AF: 0.630 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.014
DANN	Benign	0.36

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: rs9331908; hg19: chr8-27463618;