ENST00000185206.12:c.540+4683G>A

Variant names:

• chr6-46075020-C-T
• rs7744030
• ENST00000185206.12:c.540+4683G>A

Variant summary

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

The ENST00000185206.12(CLIC5):​c.540+4683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,102 control chromosomes in the GnomAD database, including 11,543 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 0.38 (11543 hom., cov: 33)
• Consequence: CLIC5 ENST00000185206.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_001114086.2	c.540+4683G>A		intron_variant	Intron 1 of 5		NP_001107558.1
CLIC5	NM_001370650.1	c.540+4683G>A		intron_variant	Intron 2 of 6		NP_001357579.1
CLIC5	NM_001370649.1	c.-55+54484G>A		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+4683G>A		intron_variant	Intron 1 of 5	1		ENSP00000185206.6

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58504 AN: 151984 Hom.: 11537 Cov.: 33

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.385 AC: 58538 AN: 152102 Hom.: 11543 Cov.: 33 AF XY: 0.382 AC XY: 28370 AN XY: 74354

African (AFR) AF: 0.412 AC: 17105 AN: 41472

American (AMR) AF: 0.370 AC: 5651 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3468

East Asian (EAS) AF: 0.150 AC: 777 AN: 5184

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4818

European-Finnish (FIN) AF: 0.362 AC: 3833 AN: 10578

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26368 AN: 67990

Other (OTH) AF: 0.408 AC: 858 AN: 2104

Alfa AF: 0.386 Hom.: 1718

Bravo AF: 0.387

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.30
DANN	Benign	0.44
PhyloP100		-0.40
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: rs7744030; hg19: chr6-46042757; COSMIC: COSV51755942;