rs3777585

Positions:

• chr6-45951232-C-T

Variant summary

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

The NM_016929.5(CLIC5):​c.174-1851G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,136 control chromosomes in the GnomAD database, including 2,663 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 0.17 (2663 hom., cov: 32)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.174-1851G>A		intron_variant		ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12	c.174-1851G>A		intron_variant		1	NM_016929.5	ENSP00000344165	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26046 AN: 152018 Hom.: 2666 Cov.: 32

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.171 AC: 26043 AN: 152136 Hom.: 2663 Cov.: 32 AF XY: 0.170 AC XY: 12613 AN XY: 74372

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.190

Alfa AF: 0.217 Hom.: 5036

Bravo AF: 0.165

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.56

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: rs3777585; hg19: chr6-45918969;