Variant rs13494 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001831.4(CLU):c.1187C>T(p.Ser396Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,614,136 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0083 ( 21 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 18 hom. )

Consequence

CLU
NM_001831.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.82

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028432608).

BP6

Variant 8-27598613-G-A is Benign according to our data. Variant chr8-27598613-G-A is described in ClinVar as [Benign]. Clinvar id is 716148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00827 (1259/152324) while in subpopulation AFR AF= 0.0288 (1198/41566). AF 95% confidence interval is 0.0275. There are 21 homozygotes in gnomad4. There are 606 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLU	NM_001831.4 linkuse as main transcript	c.1187C>T	p.Ser396Leu	missense_variant	8/9	ENST00000316403.15	NP_001822.3
CLU	NR_038335.2 linkuse as main transcript	n.1442C>T		non_coding_transcript_exon_variant	8/9
CLU	NR_045494.1 linkuse as main transcript	n.1367C>T		non_coding_transcript_exon_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 linkuse as main transcript	c.1187C>T	p.Ser396Leu	missense_variant	8/9	1	NM_001831.4	ENSP00000315130	P1	P10909-1

Frequencies

GnomAD3 genomes

AF:

0.00827

AC:

1258

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00195

AC:

491

AN:

251350

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0283

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000799

AC:

1168

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000711

AC XY:

517

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0288

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.00827

AC:

1259

AN:

152324

Hom.:

Cov.:

AF XY:

0.00814

AC XY:

606

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0288

Gnomad4 AMR

AF:

0.00287

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.00929

ESP6500AA

AF:

0.0315

AC:

139

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00257

AC:

312

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

T;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.81

.;.;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.042

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.066

B;B;B

Vest4

0.17

MVP

0.30

MPC

0.45

ClinPred

0.011

GERP RS

3.1

Varity_R

0.037

gMVP

0.19

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