6-45957230-A-G

Variant names:

• chr6-45957230-A-G
• rs4714892
• NM_016929.5:c.64-1986T>C

Variant summary

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

The NM_016929.5(CLIC5):​c.64-1986T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 151,756 control chromosomes in the GnomAD database, including 53,723 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 0.84 (53723 hom., cov: 32)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.64-1986T>C		intron_variant	Intron 1 of 5	ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12	c.64-1986T>C		intron_variant	Intron 1 of 5	1	NM_016929.5	ENSP00000344165.6

Frequencies

GnomAD3 genomes AF: 0.837 AC: 126952 AN: 151634 Hom.: 53681 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.837 AC: 127056 AN: 151756 Hom.: 53723 Cov.: 32 AF XY: 0.831 AC XY: 61676 AN XY: 74192

African (AFR) AF: 0.775 AC: 31872 AN: 41128

American (AMR) AF: 0.829 AC: 12655 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3124 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2530 AN: 5186

South Asian (SAS) AF: 0.731 AC: 3521 AN: 4814

European-Finnish (FIN) AF: 0.883 AC: 9329 AN: 10570

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.899 AC: 61111 AN: 68012

Other (OTH) AF: 0.846 AC: 1784 AN: 2108

Alfa AF: 0.877 Hom.: 29974

Bravo AF: 0.830

Asia WGS AF: 0.644 AC: 2237 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.2
DANN	Benign	0.75
PhyloP100		-0.23
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: rs4714892; hg19: chr6-45924967;