Variant 6-45912748-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016929.5(CLIC5):c.588+1480T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00859 in 1,518,520 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 81 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 336 hom. )

Consequence

CLIC5
NM_016929.5 intron

Scores

Splicing: ADA: 0.00005694

Clinical Significance

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

Conservation

PhyloP100: 0.493

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-45912748-A-G is Benign according to our data. Variant chr6-45912748-A-G is described in ClinVar as [Benign]. Clinvar id is 517543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC5	NM_016929.5 linkuse as main transcript	c.588+1480T>C		intron_variant		ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12 linkuse as main transcript	c.588+1480T>C		intron_variant		1	NM_016929.5	ENSP00000344165	P1	Q9NZA1-2

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2954

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0513

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0707

Gnomad SAS

AF:

0.0271

Gnomad FIN

AF:

0.00847

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0233

AC:

3211

AN:

137778

Hom.:

100

AF XY:

0.0215

AC XY:

1602

AN XY:

74604

show subpopulations

Gnomad AFR exome

AF:

0.0341

Gnomad AMR exome

AF:

0.0666

Gnomad ASJ exome

AF:

0.000120

Gnomad EAS exome

AF:

0.0625

Gnomad SAS exome

AF:

0.0242

Gnomad FIN exome

AF:

0.00571

Gnomad NFE exome

AF:

0.000813

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.00737

AC:

10076

AN:

1366256

Hom.:

336

Cov.:

AF XY:

0.00762

AC XY:

5147

AN XY:

675404

show subpopulations

Gnomad4 AFR exome

AF:

0.0347

Gnomad4 AMR exome

AF:

0.0618

Gnomad4 ASJ exome

AF:

0.0000798

Gnomad4 EAS exome

AF:

0.0978

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.00583

Gnomad4 NFE exome

AF:

0.000482

Gnomad4 OTH exome

AF:

0.00957

GnomAD4 genome

AF:

0.0195

AC:

2962

AN:

152264

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

1585

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0361

Gnomad4 AMR

AF:

0.0513

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0708

Gnomad4 SAS

AF:

0.0269

Gnomad4 FIN

AF:

0.00847

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.00767

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.0360

AC:

127

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

c.589-9T>C in intron 5 of CLIC5: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 5.73% (11/192) of E ast Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs75878754). -

CLIC5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 24, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.4

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000057

dbscSNV1_RF

Benign

0.0

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