Variant 6-45903262-CAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_016929.5(CLIC5):c.589-9_589-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,573,906 control chromosomes in the GnomAD database, including 111,011 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 8909 hom., cov: 0)

Exomes 𝑓: 0.38 ( 102102 hom. )

Consequence

CLIC5
NM_016929.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.51

Variant links:

Genes affected

CLIC5 (HGNC:13517): (chloride intracellular channel 5) This gene encodes a member of the chloride intracellular channel (CLIC) family of chloride ion channels. The encoded protein associates with actin-based cytoskeletal structures and may play a role in multiple processes including hair cell stereocilia formation, myoblast proliferation and glomerular podocyte and endothelial cell maintenance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

CLIC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 6-45903262-CAG-C is Benign according to our data. Variant chr6-45903262-CAG-C is described in ClinVar as [Benign]. Clinvar id is 506168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC5	NM_016929.5 linkuse as main transcript	c.589-9_589-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000339561.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000339561.12 linkuse as main transcript	c.589-9_589-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016929.5	P1	Q9NZA1-2

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51253

AN:

151752

Hom.:

8905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.354

AC:

75576

AN:

213610

Hom.:

13882

AF XY:

0.363

AC XY:

41223

AN XY:

113578

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.445

Gnomad SAS exome

AF:

0.401

Gnomad FIN exome

AF:

0.382

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.376

AC:

534338

AN:

1422036

Hom.:

102102

AF XY:

0.377

AC XY:

264972

AN XY:

702708

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.396

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.381

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.338

AC:

51274

AN:

151870

Hom.:

8909

Cov.:

AF XY:

0.338

AC XY:

25083

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.263

Gnomad4 AMR

AF:

0.281

Gnomad4 ASJ

AF:

0.367

Gnomad4 EAS

AF:

0.456

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.352

Alfa

AF:

0.348

Hom.:

1740

Bravo

AF:

0.326

Asia WGS

AF:

0.427

AC:

1484

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Sep 25, 2017

c.1066-9_1066-8delCT in intron 5 of CLIC5: This variant is not expected to have clinical significance because it has been identified in 44.4% (8056/18162) of Ea st Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.b roadinstitute.org/; dbSNP rs35735653). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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