rs3216167

Positions:

• chr8-27604255-CA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001831.4(CLU):​c.934+35del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6590 hom., cov: 20)
  • Exomes 𝑓: 0.30 (65820 hom.)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.891

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.934+35del		intron_variant		ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.1189+35del		intron_variant, non_coding_transcript_variant
CLU	NR_045494.1	n.1114+35del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.934+35del		intron_variant		1	NM_001831.4	ENSP00000315130	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42458 AN: 151888 Hom.: 6584 Cov.: 20

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.275

GnomAD3 exomes AF: 0.340 AC: 84489 AN: 248624 Hom.: 15640 AF XY: 0.336 AC XY: 45247 AN XY: 134488

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.515

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.462

Gnomad SAS exome AF: 0.386

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.319

GnomAD4 exome AF: 0.299 AC: 417669 AN: 1399150 Hom.: 65820 Cov.: 0 AF XY: 0.301 AC XY: 210643 AN XY: 699742

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.279 AC: 42477 AN: 152006 Hom.: 6590 Cov.: 20 AF XY: 0.286 AC XY: 21264 AN XY: 74292

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.281

Alfa AF: 0.171 Hom.: 742

Bravo AF: 0.277

Asia WGS AF: 0.441 AC: 1533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3216167; hg19: chr8-27461772; COSMIC: COSV57067062; COSMIC: COSV57067062;