8-27597597-A-G

Variant names:

• chr8-27597597-A-G
• rs9331942
• NM_001831.4:c.*644T>C

Variant summary

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

The NM_001831.4(CLU):​c.*644T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 454,096 control chromosomes in the GnomAD database, including 1,944 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 0.059 (546 hom., cov: 32)
  • Exomes 𝑓: 0.065 (1398 hom.)
• Consequence: CLU NM_001831.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 10 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]

ENSG00000300853 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 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.*644T>C		3_prime_UTR	Exon 9 of 9	NP_001822.3
	CLU	NR_038335.2		n.2249T>C		non_coding_transcript_exon	Exon 9 of 9
	CLU	NR_045494.1		n.2174T>C		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLU	ENST00000316403.15	TSL:1 MANE Select	c.*644T>C		3_prime_UTR	Exon 9 of 9	ENSP00000315130.10
	CLU	ENST00000405140.7	TSL:1	c.*644T>C		downstream_gene	N/A	ENSP00000385419.3
	ENSG00000300853	ENST00000774578.1		n.*38A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9060 AN: 152184 Hom.: 547 Cov.: 32

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0468

GnomAD2 exomes AF: 0.0740 AC: 9699 AN: 131036 AF XY: 0.0807

Gnomad AFR exome AF: 0.0887

Gnomad AMR exome AF: 0.0115

Gnomad ASJ exome AF: 0.0252

Gnomad EAS exome AF: 0.315

Gnomad FIN exome AF: 0.0873

Gnomad NFE exome AF: 0.0282

Gnomad OTH exome AF: 0.0427

GnomAD4 exome AF: 0.0649 AC: 19574 AN: 301794 Hom.: 1398 Cov.: 0 AF XY: 0.0737 AC XY: 12674 AN XY: 171996

African (AFR) AF: 0.0883 AC: 755 AN: 8554

American (AMR) AF: 0.0117 AC: 318 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 295 AN: 10786

East Asian (EAS) AF: 0.316 AC: 2907 AN: 9210

South Asian (SAS) AF: 0.147 AC: 8779 AN: 59650

European-Finnish (FIN) AF: 0.0828 AC: 1024 AN: 12364

Middle Eastern (MID) AF: 0.0278 AC: 32 AN: 1150

European-Non Finnish (NFE) AF: 0.0297 AC: 4720 AN: 158764

Other (OTH) AF: 0.0530 AC: 744 AN: 14042

GnomAD4 genome AF: 0.0595 AC: 9060 AN: 152302 Hom.: 546 Cov.: 32 AF XY: 0.0642 AC XY: 4779 AN XY: 74482

African (AFR) AF: 0.0800 AC: 3324 AN: 41546

American (AMR) AF: 0.0176 AC: 269 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1584 AN: 5182

South Asian (SAS) AF: 0.146 AC: 706 AN: 4822

European-Finnish (FIN) AF: 0.0925 AC: 982 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0276 AC: 1879 AN: 68032

Other (OTH) AF: 0.0454 AC: 96 AN: 2116

Alfa AF: 0.0457 Hom.: 600

Bravo AF: 0.0556

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.52
PhyloP100		-1.4
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: rs9331942; hg19: chr8-27455114;