6-45912574-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016929.5(CLIC5):c.588+1654A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,425,058 control chromosomes in the GnomAD database, including 12,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (4068 hom., cov: 33)
  • Exomes 𝑓: 0.097 (8050 hom.)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-45912574-T-C is Benign according to our data. Variant chr6-45912574-T-C is described in ClinVar as [Benign]. Clinvar id is 1270644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC5	NM_016929.5	c.588+1654A>G		intron_variant		ENST00000339561.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000339561.12	c.588+1654A>G		intron_variant		1	NM_016929.5	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27660 AN: 152054 Hom.: 4049 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.0966 AC: 123014 AN: 1272886 Hom.: 8050 Cov.: 18 AF XY: 0.0965 AC XY: 60432 AN XY: 626240

Gnomad4 AFR exome AF: 0.413

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.0383

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.0854

Gnomad4 NFE exome AF: 0.0813

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.182 AC: 27728 AN: 152172 Hom.: 4068 Cov.: 33 AF XY: 0.183 AC XY: 13629 AN XY: 74420

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0920

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.152

Alfa AF: 0.103 Hom.: 1705

Bravo AF: 0.196

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.021
Dann	Benign	0.50

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: rs6458477; hg19: chr6-45880311;