Genetic Variant NM_001831.4:c.1165-101A>G (chr8-27598736-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001831.4(CLU):c.1165-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,137,980 control chromosomes in the GnomAD database, including 225,366 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 0.69 ( 37777 hom., cov: 32)

Exomes 𝑓: 0.61 ( 187589 hom. )

Consequence

CLU
NM_001831.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.327

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 (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4 link	c.1165-101A>G	intron_variant	Intron 7 of 8	ENST00000316403.15	NP_001822.3	P10909-1
CLU	NR_038335.2 link	n.1420-101A>G	intron_variant	Intron 7 of 8
CLU	NR_045494.1 link	n.1345-101A>G	intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 link	c.1165-101A>G		intron_variant	Intron 7 of 8	1	NM_001831.4	ENSP00000315130.10		P10909-1

Frequencies

GnomAD3 genomes

AF:

0.692

AC:

105244

AN:

152024

Hom.:

37723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.895

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.589

Gnomad OTH

AF:

0.673

GnomAD4 exome

AF:

0.612

AC:

602855

AN:

985838

Hom.:

187589

Cov.:

AF XY:

0.613

AC XY:

312972

AN XY:

510212

show subpopulations

Gnomad4 AFR exome

AF:

0.898

Gnomad4 AMR exome

AF:

0.676

Gnomad4 ASJ exome

AF:

0.615

Gnomad4 EAS exome

AF:

0.762

Gnomad4 SAS exome

AF:

0.692

Gnomad4 FIN exome

AF:

0.583

Gnomad4 NFE exome

AF:

0.581

Gnomad4 OTH exome

AF:

0.629

GnomAD4 genome

AF:

0.692

AC:

105358

AN:

152142

Hom.:

37777

Cov.:

AF XY:

0.693

AC XY:

51496

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.895

Gnomad4 AMR

AF:

0.673

Gnomad4 ASJ

AF:

0.607

Gnomad4 EAS

AF:

0.786

Gnomad4 SAS

AF:

0.702

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.588

Gnomad4 OTH

AF:

0.675

Alfa

AF:

0.614

Hom.:

36354

Bravo

AF:

0.710

Asia WGS

AF:

0.745

AC:

2588

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.8

DANN

Benign

0.36

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over