rs2095771

chr6-45936895-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016929.5(CLIC5):c.406+4652G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,842 control chromosomes in the GnomAD database, including 3,861 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 0.20 (3861 hom., cov: 31)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC5	NM_016929.5	c.406+4652G>T		intron_variant		ENST00000339561.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000339561.12	c.406+4652G>T		intron_variant		1	NM_016929.5	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30559 AN: 151724 Hom.: 3867 Cov.: 31

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.201 AC: 30546 AN: 151842 Hom.: 3861 Cov.: 31 AF XY: 0.200 AC XY: 14846 AN XY: 74208

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.224

Alfa AF: 0.256 Hom.: 2702

Bravo AF: 0.191

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	11
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs2095771; hg19: chr6-45904632;