chr6-45951232-C-T

Variant names:

• chr6-45951232-C-T
• rs3777585
• NM_016929.5:c.174-1851G>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.174-1851G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,136 control chromosomes in the GnomAD database, including 2,663 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 0.17 (2663 hom., cov: 32)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• 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):

• 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

ENSG00000302748 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.174-1851G>A		intron_variant	Intron 2 of 5	ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12	c.174-1851G>A		intron_variant	Intron 2 of 5	1	NM_016929.5	ENSP00000344165.6

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26046 AN: 152018 Hom.: 2666 Cov.: 32

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.171 AC: 26043 AN: 152136 Hom.: 2663 Cov.: 32 AF XY: 0.170 AC XY: 12613 AN XY: 74372

African (AFR) AF: 0.0667 AC: 2771 AN: 41534

American (AMR) AF: 0.191 AC: 2918 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3468

East Asian (EAS) AF: 0.148 AC: 764 AN: 5176

South Asian (SAS) AF: 0.216 AC: 1038 AN: 4808

European-Finnish (FIN) AF: 0.182 AC: 1920 AN: 10578

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15136 AN: 67962

Other (OTH) AF: 0.190 AC: 400 AN: 2110

Alfa AF: 0.211 Hom.: 6061

Bravo AF: 0.165

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-0.0060
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: rs3777585; hg19: chr6-45918969;