6-45911327-C-T

Variant names:

• chr6-45911327-C-T
• rs9367228
• NM_016929.5:c.588+2901G>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.588+2901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,040 control chromosomes in the GnomAD database, including 9,019 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 0.34 (9019 hom., cov: 32)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 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.588+2901G>A		intron	N/A	NP_058625.2	Q53G01
	CLIC5	NM_001114086.2		c.1065+2901G>A		intron	N/A	NP_001107558.1	Q9NZA1-1
	CLIC5	NM_001370650.1		c.1065+2901G>A		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.588+2901G>A		intron	N/A	ENSP00000344165.6	Q9NZA1-2
	CLIC5	ENST00000185206.12	TSL:1	c.1065+2901G>A		intron	N/A	ENSP00000185206.6	Q9NZA1-1
	CLIC5	ENST00000644324.1		c.623+2451G>A		intron	N/A	ENSP00000495186.1	A0A2R8Y615

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51524 AN: 151922 Hom.: 9015 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.339 AC: 51545 AN: 152040 Hom.: 9019 Cov.: 32 AF XY: 0.340 AC XY: 25247 AN XY: 74308

African (AFR) AF: 0.264 AC: 10942 AN: 41466

American (AMR) AF: 0.285 AC: 4360 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3472

East Asian (EAS) AF: 0.457 AC: 2358 AN: 5158

South Asian (SAS) AF: 0.409 AC: 1971 AN: 4816

European-Finnish (FIN) AF: 0.381 AC: 4024 AN: 10566

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

European-Non Finnish (NFE) AF: 0.375 AC: 25501 AN: 67958

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.341 Hom.: 1556

Bravo AF: 0.327

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9367228; hg19: chr6-45879064;