6-45927943-T-G

Variant names:

• chr6-45927943-T-G
• rs4714890
• NM_016929.5:c.407-13534A>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.407-13534A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,962 control chromosomes in the GnomAD database, including 10,123 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 0.36 (10123 hom., cov: 32)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• 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 (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.407-13534A>C		intron_variant	Intron 4 of 5	ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12	c.407-13534A>C		intron_variant	Intron 4 of 5	1	NM_016929.5	ENSP00000344165.6

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54845 AN: 151844 Hom.: 10106 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.361 AC: 54907 AN: 151962 Hom.: 10123 Cov.: 32 AF XY: 0.361 AC XY: 26784 AN XY: 74268

African (AFR) AF: 0.423 AC: 17505 AN: 41420

American (AMR) AF: 0.344 AC: 5250 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2525 AN: 5148

South Asian (SAS) AF: 0.412 AC: 1987 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2913 AN: 10558

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22262 AN: 67972

Other (OTH) AF: 0.362 AC: 758 AN: 2096

Alfa AF: 0.337 Hom.: 13797

Bravo AF: 0.369

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.072
DANN	Benign	0.39
PhyloP100		-1.8
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: rs4714890; hg19: chr6-45895680;