rs3831297

Variant names:

• chr6-45903262-CAG-C
• rs3831297
• NM_016929.5:c.589-9_589-8delCT

Your query was ambiguous. Multiple possible variants found:

• chr6-45903262-CAG-C
• chr6-45903262-CAG-CAGAG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_016929.5(CLIC5):​c.589-9_589-8delCT variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,573,906 control chromosomes in the GnomAD database, including 111,011 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8909 hom., cov: 0)
  • Exomes 𝑓: 0.38 (102102 hom.)
• Consequence: CLIC5 NM_016929.5 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 8.51
• 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):

• 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 -16 ACMG points.

• BP6: Variant 6-45903262-CAG-C is Benign according to our data. Variant chr6-45903262-CAG-C is described in ClinVar as Benign. ClinVar VariationId is 506168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 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.589-9_589-8delCT		splice_region intron	N/A	NP_058625.2	Q53G01
	CLIC5	NM_001114086.2		c.1066-9_1066-8delCT		splice_region intron	N/A	NP_001107558.1	Q9NZA1-1
	CLIC5	NM_001370650.1		c.1066-9_1066-8delCT		splice_region 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.589-9_589-8delCT		splice_region intron	N/A	ENSP00000344165.6	Q9NZA1-2
	CLIC5	ENST00000185206.12	TSL:1	c.1066-9_1066-8delCT		splice_region intron	N/A	ENSP00000185206.6	Q9NZA1-1
	CLIC5	ENST00000644324.1		c.623+10514_623+10515delCT		intron	N/A	ENSP00000495186.1	A0A2R8Y615

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51253 AN: 151752 Hom.: 8905 Cov.: 0

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.353

GnomAD2 exomes AF: 0.354 AC: 75576 AN: 213610 AF XY: 0.363

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.445

Gnomad FIN exome AF: 0.382

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.376 AC: 534338 AN: 1422036 Hom.: 102102 AF XY: 0.377 AC XY: 264972 AN XY: 702708

African (AFR) AF: 0.261 AC: 8524 AN: 32670

American (AMR) AF: 0.219 AC: 9057 AN: 41272

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 8671 AN: 23242

East Asian (EAS) AF: 0.440 AC: 17253 AN: 39220

South Asian (SAS) AF: 0.396 AC: 30976 AN: 78184

European-Finnish (FIN) AF: 0.386 AC: 20002 AN: 51752

Middle Eastern (MID) AF: 0.358 AC: 1991 AN: 5560

European-Non Finnish (NFE) AF: 0.381 AC: 416006 AN: 1091364

Other (OTH) AF: 0.372 AC: 21858 AN: 58772

GnomAD4 genome AF: 0.338 AC: 51274 AN: 151870 Hom.: 8909 Cov.: 0 AF XY: 0.338 AC XY: 25083 AN XY: 74188

African (AFR) AF: 0.263 AC: 10914 AN: 41430

American (AMR) AF: 0.281 AC: 4297 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2349 AN: 5148

South Asian (SAS) AF: 0.410 AC: 1972 AN: 4810

European-Finnish (FIN) AF: 0.380 AC: 3989 AN: 10504

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25371 AN: 67932

Other (OTH) AF: 0.352 AC: 741 AN: 2108

Alfa AF: 0.348 Hom.: 1740

Bravo AF: 0.326

Asia WGS AF: 0.427 AC: 1484 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.5
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: rs3831297; hg19: chr6-45870999; COSMIC: COSV51755387;