8-27597925-T-C

Variant names:

• chr8-27597925-T-C
• rs3087554
• NM_001831.4:c.*316A>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.*316A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 594,824 control chromosomes in the GnomAD database, including 13,937 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 (3417 hom., cov: 31)
  • Exomes 𝑓: 0.21 (10520 hom.)
• Consequence: CLU NM_001831.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 27 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 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.*316A>G		3_prime_UTR	Exon 9 of 9	NP_001822.3
	CLU	NR_038335.2		n.1921A>G		non_coding_transcript_exon	Exon 9 of 9
	CLU	NR_045494.1		n.1846A>G		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.*316A>G		3_prime_UTR	Exon 9 of 9	ENSP00000315130.10
	CLU	ENST00000405140.7	TSL:1	c.*316A>G		3_prime_UTR	Exon 9 of 9	ENSP00000385419.3
	CLU	ENST00000523500.5	TSL:1	c.*316A>G		downstream_gene	N/A	ENSP00000429620.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31350 AN: 151802 Hom.: 3414 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.230 AC: 30069 AN: 130956 AF XY: 0.225

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.333

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.262

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.207 AC: 91699 AN: 442904 Hom.: 10520 Cov.: 0 AF XY: 0.210 AC XY: 51257 AN XY: 243780

African (AFR) AF: 0.207 AC: 2726 AN: 13168

American (AMR) AF: 0.322 AC: 10111 AN: 31388

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 2541 AN: 16422

East Asian (EAS) AF: 0.274 AC: 5728 AN: 20922

South Asian (SAS) AF: 0.269 AC: 16385 AN: 60888

European-Finnish (FIN) AF: 0.210 AC: 4733 AN: 22586

Middle Eastern (MID) AF: 0.142 AC: 279 AN: 1968

European-Non Finnish (NFE) AF: 0.177 AC: 44672 AN: 251788

Other (OTH) AF: 0.190 AC: 4524 AN: 23774

GnomAD4 genome AF: 0.207 AC: 31373 AN: 151920 Hom.: 3417 Cov.: 31 AF XY: 0.211 AC XY: 15633 AN XY: 74258

African (AFR) AF: 0.212 AC: 8794 AN: 41396

American (AMR) AF: 0.281 AC: 4282 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1411 AN: 5164

South Asian (SAS) AF: 0.282 AC: 1354 AN: 4800

European-Finnish (FIN) AF: 0.213 AC: 2253 AN: 10568

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12194 AN: 67948

Other (OTH) AF: 0.190 AC: 400 AN: 2108

Alfa AF: 0.186 Hom.: 2315

Bravo AF: 0.209

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.29
PhyloP100		-1.9
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: rs3087554; hg19: chr8-27455442;