6-46075020-C-T

Position:

• chr6-46075020-C-T

Variant summary

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

The ENST00000185206.12(CLIC5):​c.540+4683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,102 control chromosomes in the GnomAD database, including 11,543 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 0.38 (11543 hom., cov: 33)
• Consequence: CLIC5 ENST00000185206.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC5	NM_001114086.2	c.540+4683G>A		intron_variant
CLIC5	NM_001370649.1	c.-55+54484G>A		intron_variant
CLIC5	NM_001370650.1	c.540+4683G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000185206.12	c.540+4683G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58504 AN: 151984 Hom.: 11537 Cov.: 33

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.385 AC: 58538 AN: 152102 Hom.: 11543 Cov.: 33 AF XY: 0.382 AC XY: 28370 AN XY: 74354

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.408

Alfa AF: 0.385 Hom.: 1656

Bravo AF: 0.387

Asia WGS AF: 0.250 AC: 869 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	0.30
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7744030; hg19: chr6-46042757; COSMIC: COSV51755942;