rs3777580

chr6-45942727-A-Cchr6-45942727-A-Gchr6-45942727-A-T

Variant summary

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

The NM_016929.5(CLIC5):c.300-1074T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,122 control chromosomes in the GnomAD database, including 18,406 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 0.46 (18406 hom., cov: 33)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC5	NM_016929.5	c.300-1074T>G		intron_variant		ENST00000339561.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000339561.12	c.300-1074T>G		intron_variant		1	NM_016929.5	P1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70593 AN: 152004 Hom.: 18381 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.465 AC: 70674 AN: 152122 Hom.: 18406 Cov.: 33 AF XY: 0.466 AC XY: 34631 AN XY: 74362

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.455

Alfa AF: 0.376 Hom.: 10632

Bravo AF: 0.478

Asia WGS AF: 0.631 AC: 2193 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.3
Dann	Benign	0.37

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: rs3777580; hg19: chr6-45910464;