Variant 8-27604964-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001831.4(CLU):c.789T>C(p.His263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,613,754 control chromosomes in the GnomAD database, including 302,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.61 ( 28231 hom., cov: 31)

Exomes 𝑓: 0.61 ( 274300 hom. )

Consequence

CLU
NM_001831.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.467

Variant links:

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]

CLU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 8-27604964-A-G is Benign according to our data. Variant chr8-27604964-A-G is described in ClinVar as [Benign]. Clinvar id is 3060904.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.467 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLU	NM_001831.4 linkuse as main transcript	c.789T>C	p.His263=	synonymous_variant	5/9	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2 linkuse as main transcript	n.1044T>C		non_coding_transcript_exon_variant	5/9
CLU	NR_045494.1 linkuse as main transcript	n.969T>C		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 linkuse as main transcript	c.789T>C	p.His263=	synonymous_variant	5/9	1	NM_001831.4	ENSP00000315130	P1	P10909-1

Frequencies

GnomAD3 genomes

AF:

0.608

AC:

92335

AN:

151818

Hom.:

28209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.705

Gnomad FIN

AF:

0.597

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.616

GnomAD3 exomes

AF:

0.636

AC:

160034

AN:

251456

Hom.:

51304

AF XY:

0.638

AC XY:

86746

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.677

Gnomad ASJ exome

AF:

0.600

Gnomad EAS exome

AF:

0.782

Gnomad SAS exome

AF:

0.700

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.630

GnomAD4 exome

AF:

0.611

AC:

893139

AN:

1461818

Hom.:

274300

Cov.:

AF XY:

0.614

AC XY:

446328

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.569

Gnomad4 AMR exome

AF:

0.670

Gnomad4 ASJ exome

AF:

0.598

Gnomad4 EAS exome

AF:

0.763

Gnomad4 SAS exome

AF:

0.695

Gnomad4 FIN exome

AF:

0.594

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.618

GnomAD4 genome

AF:

0.608

AC:

92411

AN:

151936

Hom.:

28231

Cov.:

AF XY:

0.612

AC XY:

45465

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.649

Gnomad4 ASJ

AF:

0.590

Gnomad4 EAS

AF:

0.788

Gnomad4 SAS

AF:

0.705

Gnomad4 FIN

AF:

0.597

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.618

Alfa

AF:

0.608

Hom.:

22633

Bravo

AF:

0.612

Asia WGS

AF:

0.726

AC:

2523

AN:

3478

EpiCase

AF:

0.613

EpiControl

AF:

0.606

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLU-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.39

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over