NM_001370650.1:c.-45-2811T>C

Variant names:

• chr6-46083098-A-G
• rs9395152
• NM_001370650.1:c.-45-2811T>C

Variant summary

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

The NM_001370650.1(CLIC5):​c.-45-2811T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,268 control chromosomes in the GnomAD database, including 2,204 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 0.16 (2204 hom., cov: 33)
• Consequence: CLIC5 NM_001370650.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88
• 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

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 (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_001370650.1	c.-45-2811T>C		intron_variant	Intron 1 of 6		NP_001357579.1
CLIC5	NM_001370649.1	c.-55+46406T>C		intron_variant	Intron 1 of 5		NP_001357578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24407 AN: 152150 Hom.: 2201 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.160 AC: 24429 AN: 152268 Hom.: 2204 Cov.: 33 AF XY: 0.163 AC XY: 12168 AN XY: 74470

African (AFR) AF: 0.128 AC: 5327 AN: 41554

American (AMR) AF: 0.136 AC: 2082 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 817 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1587 AN: 5180

South Asian (SAS) AF: 0.336 AC: 1624 AN: 4830

European-Finnish (FIN) AF: 0.154 AC: 1633 AN: 10614

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10791 AN: 68002

Other (OTH) AF: 0.160 AC: 339 AN: 2114

Alfa AF: 0.167 Hom.: 1305

Bravo AF: 0.153

Asia WGS AF: 0.331 AC: 1150 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	0.026
DANN	Benign	0.20
PhyloP100		-3.9

Splicing

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

Other links and lift over

dbSNP: rs9395152; hg19: chr6-46050835;