rs9381423

Variant names:

• chr6-46079532-T-C
• rs9381423
• ENST00000185206.12:c.540+171A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000185206.12(CLIC5):​c.540+171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,226 control chromosomes in the GnomAD database, including 2,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2573 hom., cov: 33)
• Consequence: CLIC5 ENST00000185206.12 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.901
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-46079532-T-C is Benign according to our data. Variant chr6-46079532-T-C is described in ClinVar as Benign. ClinVar VariationId is 1285748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_001114086.2	c.540+171A>G		intron_variant	Intron 1 of 5		NP_001107558.1
CLIC5	NM_001370650.1	c.540+171A>G		intron_variant	Intron 2 of 6		NP_001357579.1
CLIC5	NM_001370649.1	c.-55+49972A>G		intron_variant	Intron 1 of 5		NP_001357578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000185206.12	c.540+171A>G		intron_variant	Intron 1 of 5	1		ENSP00000185206.6

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26396 AN: 152108 Hom.: 2571 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.174 AC: 26418 AN: 152226 Hom.: 2573 Cov.: 33 AF XY: 0.176 AC XY: 13113 AN XY: 74434

African (AFR) AF: 0.166 AC: 6897 AN: 41534

American (AMR) AF: 0.140 AC: 2145 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1732 AN: 5180

South Asian (SAS) AF: 0.335 AC: 1615 AN: 4826

European-Finnish (FIN) AF: 0.155 AC: 1642 AN: 10612

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10984 AN: 67992

Other (OTH) AF: 0.167 AC: 352 AN: 2114

Alfa AF: 0.173 Hom.: 1684

Bravo AF: 0.168

Asia WGS AF: 0.345 AC: 1198 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9381423; hg19: chr6-46047269;