rs3087554

Positions:

• chr8-27597925-T-C
• chr8-27597925-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.*316A>G		3_prime_UTR_variant	9/9	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.1921A>G		non_coding_transcript_exon_variant	9/9
CLU	NR_045494.1	n.1846A>G		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.*316A>G		3_prime_UTR_variant	9/9	1	NM_001831.4	ENSP00000315130	P1
CLU	ENST00000405140.7	c.*316A>G		3_prime_UTR_variant	9/9	1		ENSP00000385419	P1

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

GnomAD3 exomes AF: 0.230 AC: 30069 AN: 130956 Hom.: 3840 AF XY: 0.225 AC XY: 16103 AN XY: 71468

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 SAS exome AF: 0.272

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

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.190

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

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.190

Alfa AF: 0.184 Hom.: 1664

Bravo AF: 0.209

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs3087554; hg19: chr8-27455442;