6-45912436-A-G

Position:

• chr6-45912436-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016929.5(CLIC5):​c.588+1792T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,174,364 control chromosomes in the GnomAD database, including 473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (79 hom., cov: 33)
  • Exomes 𝑓: 0.026 (394 hom.)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.78

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-45912436-A-G is Benign according to our data. Variant chr6-45912436-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.588+1792T>C		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+1792T>C		intron_variant		1	NM_016929.5	ENSP00000344165	P1

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4670 AN: 152186 Hom.: 78 Cov.: 33

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0262 AC: 26729 AN: 1022060 Hom.: 394 Cov.: 32 AF XY: 0.0261 AC XY: 12663 AN XY: 484742

Gnomad4 AFR exome AF: 0.0473

Gnomad4 AMR exome AF: 0.0559

Gnomad4 ASJ exome AF: 0.00914

Gnomad4 EAS exome AF: 0.00324

Gnomad4 SAS exome AF: 0.0244

Gnomad4 FIN exome AF: 0.0177

Gnomad4 NFE exome AF: 0.0261

Gnomad4 OTH exome AF: 0.0233

GnomAD4 genome AF: 0.0308 AC: 4692 AN: 152304 Hom.: 79 Cov.: 33 AF XY: 0.0307 AC XY: 2287 AN XY: 74468

Gnomad4 AFR AF: 0.0452

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00329

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0266

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0317 Hom.: 15

Bravo AF: 0.0337

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.42

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: rs72871427; hg19: chr6-45880173;