6-46040108-A-G

Position:

• chr6-46040108-A-G

Variant summary

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

The NM_001114086.2(CLIC5):​c.540+39595T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,152 control chromosomes in the GnomAD database, including 42,031 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 0.74 (42031 hom., cov: 32)
• Consequence: CLIC5 NM_001114086.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC5	NM_001114086.2	c.540+39595T>C		intron_variant			NP_001107558.1
CLIC5	NM_001370650.1	c.540+39595T>C		intron_variant			NP_001357579.1
CLIC5	NM_001370649.1	c.-54-84864T>C		intron_variant			NP_001357578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000185206.12	c.540+39595T>C		intron_variant		1		ENSP00000185206.6

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112638 AN: 152034 Hom.: 41981 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.741 AC: 112742 AN: 152152 Hom.: 42031 Cov.: 32 AF XY: 0.734 AC XY: 54587 AN XY: 74376

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.733

Alfa AF: 0.740 Hom.: 54877

Bravo AF: 0.751

Asia WGS AF: 0.580 AC: 2021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.46
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6458486; hg19: chr6-46007845;