chr8-27611345-C-G

Variant names:

• chr8-27611345-C-G
• rs9331888
• ENST00000405140.7:c.-229G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000405140.7(CLU):​c.-229G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 456,164 control chromosomes in the GnomAD database, including 24,940 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 0.28 (6681 hom., cov: 32)
  • Exomes 𝑓: 0.33 (18259 hom.)
• Consequence: CLU ENST00000405140.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 116 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 (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000405140.7. 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.-29-745G>C		intron	N/A	NP_001822.3
	CLU	NR_038335.2		n.27G>C		non_coding_transcript_exon	Exon 1 of 9
	CLU	NR_045494.1		n.151+256G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	ENST00000405140.7	TSL:1	c.-229G>C		5_prime_UTR	Exon 1 of 9	ENSP00000385419.3
	CLU	ENST00000523500.5	TSL:1	c.-774G>C		5_prime_UTR	Exon 1 of 8	ENSP00000429620.1
	CLU	ENST00000316403.15	TSL:1 MANE Select	c.-29-745G>C		intron	N/A	ENSP00000315130.10

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42705 AN: 152020 Hom.: 6673 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.279

GnomAD2 exomes AF: 0.351 AC: 47344 AN: 135074 AF XY: 0.345

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.467

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.319

GnomAD4 exome AF: 0.335 AC: 101762 AN: 304026 Hom.: 18259 Cov.: 0 AF XY: 0.337 AC XY: 58340 AN XY: 173176

African (AFR) AF: 0.168 AC: 1443 AN: 8600

American (AMR) AF: 0.503 AC: 13751 AN: 27320

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 2776 AN: 10816

East Asian (EAS) AF: 0.455 AC: 4273 AN: 9394

South Asian (SAS) AF: 0.378 AC: 22586 AN: 59674

European-Finnish (FIN) AF: 0.356 AC: 4589 AN: 12876

Middle Eastern (MID) AF: 0.272 AC: 317 AN: 1166

European-Non Finnish (NFE) AF: 0.298 AC: 47683 AN: 160038

Other (OTH) AF: 0.307 AC: 4344 AN: 14142

GnomAD4 genome AF: 0.281 AC: 42730 AN: 152138 Hom.: 6681 Cov.: 32 AF XY: 0.289 AC XY: 21512 AN XY: 74388

African (AFR) AF: 0.163 AC: 6750 AN: 41530

American (AMR) AF: 0.403 AC: 6159 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 838 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2397 AN: 5152

South Asian (SAS) AF: 0.404 AC: 1949 AN: 4824

European-Finnish (FIN) AF: 0.365 AC: 3866 AN: 10584

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19918 AN: 67970

Other (OTH) AF: 0.285 AC: 602 AN: 2110

Alfa AF: 0.292 Hom.: 1322

Bravo AF: 0.277

Asia WGS AF: 0.441 AC: 1532 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	5.5
DANN	Benign	0.64
PhyloP100		0.19
PromoterAI		0.093	Neutral
Mutation Taster		=300/0	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: rs9331888; hg19: chr8-27468862;