rs9331908

Variant names:

• chr8-27606101-C-T
• rs9331908
• NM_001831.4:c.417+253G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLU	NM_001831.4	c.417+253G>A		intron_variant	Intron 4 of 8	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.672+253G>A		intron_variant	Intron 4 of 8
CLU	NR_045494.1	n.597+253G>A		intron_variant	Intron 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.417+253G>A		intron_variant	Intron 4 of 8	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

African (AFR) AF: 0.267 AC: 11070 AN: 41454

American (AMR) AF: 0.447 AC: 6831 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 893 AN: 3466

East Asian (EAS) AF: 0.772 AC: 3989 AN: 5166

South Asian (SAS) AF: 0.552 AC: 2658 AN: 4812

European-Finnish (FIN) AF: 0.428 AC: 4509 AN: 10540

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22950 AN: 67944

Other (OTH) AF: 0.355 AC: 750 AN: 2110

Alfa AF: 0.354 Hom.: 1846

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
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9331908; hg19: chr8-27463618;