rs867231

Variant names:

• chr8-27609875-G-C
• rs867231
• NM_001831.4:c.97+600C>G

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+600C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,028 control chromosomes in the GnomAD database, including 3,267 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 0.19 (3267 hom., cov: 32)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4	c.97+600C>G		intron_variant	Intron 2 of 8	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.352+600C>G		intron_variant	Intron 2 of 8
CLU	NR_045494.1	n.277+600C>G		intron_variant	Intron 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.97+600C>G		intron_variant	Intron 2 of 8	1	NM_001831.4	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29133 AN: 151910 Hom.: 3265 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.192 AC: 29130 AN: 152028 Hom.: 3267 Cov.: 32 AF XY: 0.185 AC XY: 13765 AN XY: 74292

African (AFR) AF: 0.105 AC: 4358 AN: 41472

American (AMR) AF: 0.187 AC: 2861 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1100 AN: 3470

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5178

South Asian (SAS) AF: 0.140 AC: 676 AN: 4816

European-Finnish (FIN) AF: 0.160 AC: 1684 AN: 10530

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17679 AN: 67970

Other (OTH) AF: 0.220 AC: 465 AN: 2116

Alfa AF: 0.213 Hom.: 474

Bravo AF: 0.192

Asia WGS AF: 0.0630 AC: 222 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	3.0
DANN	Benign	0.34
PhyloP100		0.48
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: rs867231; hg19: chr8-27467392;