rs11758298

Variant names:

• chr6-45917961-C-T
• rs11758298
• NM_016929.5:c.407-3552G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016929.5(CLIC5):​c.407-3552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,270 control chromosomes in the GnomAD database, including 1,113 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 0.11 (1113 hom., cov: 33)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.407-3552G>A		intron_variant	Intron 4 of 5	ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12	c.407-3552G>A		intron_variant	Intron 4 of 5	1	NM_016929.5	ENSP00000344165.6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16094 AN: 152152 Hom.: 1113 Cov.: 33

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.106 AC: 16092 AN: 152270 Hom.: 1113 Cov.: 33 AF XY: 0.103 AC XY: 7684 AN XY: 74446

African (AFR) AF: 0.0281 AC: 1169 AN: 41568

American (AMR) AF: 0.116 AC: 1778 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5192

South Asian (SAS) AF: 0.0454 AC: 219 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1399 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10744 AN: 68014

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.122 Hom.: 811

Bravo AF: 0.0997

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.58
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11758298; hg19: chr6-45885698;