6-45911327-C-T

Position:

• chr6-45911327-C-T

Variant summary

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

The ENST00000339561.12(CLIC5):​c.588+2901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,040 control chromosomes in the GnomAD database, including 9,019 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 0.34 (9019 hom., cov: 32)
• Consequence: CLIC5 ENST00000339561.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.588+2901G>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.588+2901G>A		intron_variant		1	NM_016929.5	ENSP00000344165	P1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51524 AN: 151922 Hom.: 9015 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.339 AC: 51545 AN: 152040 Hom.: 9019 Cov.: 32 AF XY: 0.340 AC XY: 25247 AN XY: 74308

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.353

Alfa AF: 0.342 Hom.: 1519

Bravo AF: 0.327

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9367228; hg19: chr6-45879064;