Variant rs9331936 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001831.4(CLU):c.949A>C(p.Asn317His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,613,952 control chromosomes in the GnomAD database, including 1,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.061 ( 987 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 859 hom. )

Consequence

CLU
NM_001831.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014353693).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLU	NM_001831.4 linkuse as main transcript	c.949A>C	p.Asn317His	missense_variant	7/9	ENST00000316403.15
CLU	NR_038335.2 linkuse as main transcript	n.1204A>C		non_coding_transcript_exon_variant	7/9
CLU	NR_045494.1 linkuse as main transcript	n.1129A>C		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLU	ENST00000316403.15 linkuse as main transcript	c.949A>C	p.Asn317His	missense_variant	7/9	1	NM_001831.4	P1	P10909-1

Frequencies

GnomAD3 genomes

AF:

0.0612

AC:

9312

AN:

152084

Hom.:

985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.0446

GnomAD3 exomes

AF:

0.0156

AC:

3927

AN:

251356

Hom.:

358

AF XY:

0.0113

AC XY:

1542

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.00977

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000633

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00628

AC:

9185

AN:

1461750

Hom.:

859

Cov.:

AF XY:

0.00535

AC XY:

3894

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.00333

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000392

Gnomad4 OTH exome

AF:

0.0138

GnomAD4 genome

AF:

0.0613

AC:

9330

AN:

152202

Hom.:

987

Cov.:

AF XY:

0.0583

AC XY:

4339

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.213

Gnomad4 AMR

AF:

0.0225

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.0441

Alfa

AF:

0.0136

Hom.:

305

Bravo

AF:

0.0700

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.197

AC:

869

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0192

AC:

2332

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.74

.;.;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.027

D;D;D

Sift4G

Uncertain

0.045

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.077

MPC

1.4

ClinPred

0.027

GERP RS

-1.3

Varity_R

0.046

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over