NM_016929.5:c.407-2915C>A

Variant names:

• chr6-45917324-G-T
• rs4714888
• NM_016929.5:c.407-2915C>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.407-2915C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,128 control chromosomes in the GnomAD database, including 1,247 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 0.11 (1247 hom., cov: 32)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 11 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	NM_016929.5	MANE Select	c.407-2915C>A		intron	N/A	NP_058625.2
	CLIC5	NM_001114086.2		c.884-2915C>A		intron	N/A	NP_001107558.1
	CLIC5	NM_001370650.1		c.884-2915C>A		intron	N/A	NP_001357579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	ENST00000339561.12	TSL:1 MANE Select	c.407-2915C>A		intron	N/A	ENSP00000344165.6
	CLIC5	ENST00000185206.12	TSL:1	c.884-2915C>A		intron	N/A	ENSP00000185206.6
	CLIC5	ENST00000644324.1		c.407-2915C>A		intron	N/A	ENSP00000495186.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16069 AN: 152010 Hom.: 1243 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0964

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0934

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

GnomAD4 genome AF: 0.106 AC: 16089 AN: 152128 Hom.: 1247 Cov.: 32 AF XY: 0.108 AC XY: 8023 AN XY: 74394

African (AFR) AF: 0.209 AC: 8669 AN: 41454

American (AMR) AF: 0.0962 AC: 1471 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3472

East Asian (EAS) AF: 0.124 AC: 642 AN: 5176

South Asian (SAS) AF: 0.124 AC: 596 AN: 4808

European-Finnish (FIN) AF: 0.0736 AC: 781 AN: 10608

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0532 AC: 3621 AN: 68010

Other (OTH) AF: 0.0981 AC: 207 AN: 2110

Alfa AF: 0.0759 Hom.: 1106

Bravo AF: 0.110

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.49
PhyloP100		0.079
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: rs4714888; hg19: chr6-45885061;