8-27610169-C-T

Variant names:

• chr8-27610169-C-T
• rs9331896
• NM_001831.4:c.97+306G>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.97+306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,972 control chromosomes in the GnomAD database, including 24,941 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 0.57 (24941 hom., cov: 32)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 135 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4	c.97+306G>A		intron_variant	Intron 2 of 8	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.352+306G>A		intron_variant	Intron 2 of 8
CLU	NR_045494.1	n.277+306G>A		intron_variant	Intron 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.97+306G>A		intron_variant	Intron 2 of 8	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86078 AN: 151854 Hom.: 24925 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.567 AC: 86135 AN: 151972 Hom.: 24941 Cov.: 32 AF XY: 0.572 AC XY: 42502 AN XY: 74294

African (AFR) AF: 0.438 AC: 18152 AN: 41410

American (AMR) AF: 0.638 AC: 9745 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1991 AN: 3466

East Asian (EAS) AF: 0.775 AC: 3998 AN: 5156

South Asian (SAS) AF: 0.698 AC: 3365 AN: 4822

European-Finnish (FIN) AF: 0.602 AC: 6364 AN: 10570

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40541 AN: 67948

Other (OTH) AF: 0.584 AC: 1233 AN: 2112

Alfa AF: 0.586 Hom.: 47770

Bravo AF: 0.565

Asia WGS AF: 0.706 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.036
DANN	Benign	0.80
PhyloP100		-1.2
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: rs9331896; hg19: chr8-27467686;