rs3777567

chr6-45932829-G-Achr6-45932829-G-T

Variant summary

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

The NM_016929.5(CLIC5):c.406+8718C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,256 control chromosomes in the GnomAD database, including 4,902 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 0.24 (4900 hom., cov: 33)
  • Exomes 𝑓: 0.21 (2 hom.)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC5	NM_016929.5	c.406+8718C>T		intron_variant		ENST00000339561.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000339561.12	c.406+8718C>T		intron_variant		1	NM_016929.5	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36459 AN: 152058 Hom.: 4906 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.212 AC: 17 AN: 80 Hom.: 2 Cov.: 0 AF XY: 0.207 AC XY: 12 AN XY: 58

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.239 AC: 36445 AN: 152176 Hom.: 4900 Cov.: 33 AF XY: 0.240 AC XY: 17846 AN XY: 74386

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.255

Alfa AF: 0.275 Hom.: 2774

Bravo AF: 0.231

Asia WGS AF: 0.334 AC: 1160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.27
Dann	Benign	0.53

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: rs3777567; hg19: chr6-45900566;