Genetic Variant NM_016929.5:c.406+8718C>T (chr6-45932829-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016929.5(CLIC5):c.406+8718C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,256 control chromosomes in the GnomAD database, including 4,902 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 0.24 ( 4900 hom., cov: 33)

Exomes 𝑓: 0.21 ( 2 hom. )

Consequence

CLIC5
NM_016929.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.763

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 103
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CLIC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5 link	c.406+8718C>T		intron_variant	Intron 4 of 5	ENST00000339561.12	NP_058625.2	Q9NZA1-2Q53G01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12 link	c.406+8718C>T		intron_variant	Intron 4 of 5	1	NM_016929.5	ENSP00000344165.6		Q9NZA1-2

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36459

AN:

152058

Hom.:

4906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.212

AC:

AN:

Hom.:

Cov.:

AF XY:

0.207

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.203

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.239

AC:

36445

AN:

152176

Hom.:

4900

Cov.:

AF XY:

0.240

AC XY:

17846

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.128

AC:

5327

AN:

41538

American (AMR)

AF:

0.222

AC:

3395

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1017

AN:

3468

East Asian (EAS)

AF:

0.403

AC:

2081

AN:

5168

South Asian (SAS)

AF:

0.323

AC:

1555

AN:

4820

European-Finnish (FIN)

AF:

0.248

AC:

2630

AN:

10590

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19627

AN:

67976

Other (OTH)

AF:

0.255

AC:

539

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1376

2751

4127

5502

6878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.275

Hom.:

3091

Bravo

AF:

0.231

Asia WGS

AF:

0.334

AC:

1160

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.27

(source)

DANN

Benign

0.53

PhyloP100

-0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over