chr8-27600587-G-C

Variant names:

• chr8-27600587-G-C
• rs9331931
• NM_001831.4:c.935-578C>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.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
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	NM_001831.4	MANE Select	c.935-578C>G		intron	N/A	NP_001822.3
	CLU	NR_038335.2		n.1190-578C>G		intron	N/A
	CLU	NR_045494.1		n.1115-578C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	ENST00000316403.15	TSL:1 MANE Select	c.935-578C>G		intron	N/A	ENSP00000315130.10
	CLU	ENST00000405140.7	TSL:1	c.935-578C>G		intron	N/A	ENSP00000385419.3
	CLU	ENST00000523500.5	TSL:1	c.935-578C>G		intron	N/A	ENSP00000429620.1

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

African (AFR) AF: 0.177 AC: 7346 AN: 41490

American (AMR) AF: 0.188 AC: 2873 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1097 AN: 3466

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

South Asian (SAS) AF: 0.149 AC: 717 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1749 AN: 10570

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

European-Non Finnish (NFE) AF: 0.263 AC: 17871 AN: 67962

Other (OTH) AF: 0.233 AC: 493 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.61
PhyloP100		1.1
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: rs9331931; hg19: chr8-27458104;