rs2095771

Variant names:

• chr6-45936895-C-A
• rs2095771
• NM_016929.5:c.406+4652G>T

Variant summary

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

The NM_016929.5(CLIC5):​c.406+4652G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,842 control chromosomes in the GnomAD database, including 3,861 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 0.20 (3861 hom., cov: 31)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636
• Publications: 3 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):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 103

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016929.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	NM_016929.5	MANE Select	c.406+4652G>T		intron	N/A	NP_058625.2	Q53G01
	CLIC5	NM_001114086.2		c.883+4652G>T		intron	N/A	NP_001107558.1	Q9NZA1-1
	CLIC5	NM_001370650.1		c.883+4652G>T		intron	N/A	NP_001357579.1	Q9NZA1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	ENST00000339561.12	TSL:1 MANE Select	c.406+4652G>T		intron	N/A	ENSP00000344165.6	Q9NZA1-2
	CLIC5	ENST00000185206.12	TSL:1	c.883+4652G>T		intron	N/A	ENSP00000185206.6	Q9NZA1-1
	CLIC5	ENST00000644324.1		c.406+4652G>T		intron	N/A	ENSP00000495186.1	A0A2R8Y615

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30559 AN: 151724 Hom.: 3867 Cov.: 31

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.201 AC: 30546 AN: 151842 Hom.: 3861 Cov.: 31 AF XY: 0.200 AC XY: 14846 AN XY: 74208

African (AFR) AF: 0.0525 AC: 2174 AN: 41448

American (AMR) AF: 0.208 AC: 3174 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3472

East Asian (EAS) AF: 0.147 AC: 761 AN: 5162

South Asian (SAS) AF: 0.282 AC: 1342 AN: 4760

European-Finnish (FIN) AF: 0.227 AC: 2396 AN: 10534

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18953 AN: 67906

Other (OTH) AF: 0.224 AC: 472 AN: 2104

Alfa AF: 0.256 Hom.: 2991

Bravo AF: 0.191

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		0.64
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: rs2095771; hg19: chr6-45904632;