6-45919684-A-T

Position:

• chr6-45919684-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.407-5275T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,156 control chromosomes in the GnomAD database, including 5,727 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 0.26 (5727 hom., cov: 32)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.407-5275T>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.407-5275T>A		intron_variant		1	NM_016929.5	ENSP00000344165.6

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40158 AN: 152038 Hom.: 5726 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.264 AC: 40165 AN: 152156 Hom.: 5727 Cov.: 32 AF XY: 0.264 AC XY: 19659 AN XY: 74388

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.280

Alfa AF: 0.267 Hom.: 758

Bravo AF: 0.255

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.82

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: rs1416167; hg19: chr6-45887421;