chr6-46129040-T-C

Variant names:

• chr6-46129040-T-C
• rs3756804
• NM_001370650.1:c.-46+464A>G

Variant summary

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

The NM_001370650.1(CLIC5):​c.-46+464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,262 control chromosomes in the GnomAD database, including 830 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 0.097 (830 hom., cov: 32)
• Consequence: CLIC5 NM_001370650.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 3 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

ENSG00000231769 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370650.1. 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_001370650.1		c.-46+464A>G		intron	N/A	NP_001357579.1
	CLIC5	NM_001370649.1		c.-55+464A>G		intron	N/A	NP_001357578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000231769	ENST00000437249.3	TSL:3	n.235+550A>G		intron	N/A
	ENSG00000231769	ENST00000444038.4	TSL:3	n.328+464A>G		intron	N/A
	ENSG00000231769	ENST00000669498.1		n.354+464A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14712 AN: 152144 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0967 AC: 14724 AN: 152262 Hom.: 830 Cov.: 32 AF XY: 0.0996 AC XY: 7417 AN XY: 74462

African (AFR) AF: 0.141 AC: 5855 AN: 41546

American (AMR) AF: 0.0777 AC: 1189 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3472

East Asian (EAS) AF: 0.164 AC: 847 AN: 5178

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4828

European-Finnish (FIN) AF: 0.163 AC: 1727 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4543 AN: 68018

Other (OTH) AF: 0.0785 AC: 166 AN: 2114

Alfa AF: 0.0751 Hom.: 1895

Bravo AF: 0.0950

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.4
DANN	Benign	0.47
PhyloP100		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3756804; hg19: chr6-46096777;