8-27607002-T-C

Position:

• chr8-27607002-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.247-478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,100 control chromosomes in the GnomAD database, including 25,240 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 0.57 (25240 hom., cov: 33)
• Consequence: CLU NM_001831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLU	NM_001831.4	c.247-478A>G		intron_variant		ENST00000316403.15
CLU	NR_038335.2	n.502-478A>G		intron_variant, non_coding_transcript_variant
CLU	NR_045494.1	n.427-478A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLU	ENST00000316403.15	c.247-478A>G		intron_variant		1	NM_001831.4	P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86673 AN: 151982 Hom.: 25227 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.586

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.570 AC: 86726 AN: 152100 Hom.: 25240 Cov.: 33 AF XY: 0.575 AC XY: 42756 AN XY: 74348

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.589

Alfa AF: 0.607 Hom.: 55144

Bravo AF: 0.569

Asia WGS AF: 0.707 AC: 2457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
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: rs11136000; hg19: chr8-27464519;