8-27608798-T-C

Position:

• chr8-27608798-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001831.4(CLU):​c.246+140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 878,274 control chromosomes in the GnomAD database, including 182,103 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 0.68 (35540 hom., cov: 34)
  • Exomes 𝑓: 0.63 (146563 hom.)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLU	NM_001831.4	c.246+140A>G		intron_variant		ENST00000316403.15	NP_001822.3
CLU	NR_038335.2	n.501+140A>G		intron_variant, non_coding_transcript_variant
CLU	NR_045494.1	n.426+140A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15	c.246+140A>G		intron_variant		1	NM_001831.4	ENSP00000315130	P1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103068 AN: 152074 Hom.: 35497 Cov.: 34

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.633 AC: 459905 AN: 726082 Hom.: 146563 Cov.: 9 AF XY: 0.635 AC XY: 245649 AN XY: 386870

Gnomad4 AFR exome AF: 0.807

Gnomad4 AMR exome AF: 0.683

Gnomad4 ASJ exome AF: 0.603

Gnomad4 EAS exome AF: 0.740

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.640

GnomAD4 genome AF: 0.678 AC: 103169 AN: 152192 Hom.: 35540 Cov.: 34 AF XY: 0.678 AC XY: 50468 AN XY: 74388

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.670

Alfa AF: 0.626 Hom.: 49192

Bravo AF: 0.691

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.58

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: rs1532278; hg19: chr8-27466315;