rs9381423

Positions:

• chr6-46079532-T-C

Variant summary

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

The ENST00000185206.12(CLIC5):​c.540+171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,226 control chromosomes in the GnomAD database, including 2,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2573 hom., cov: 33)
• Consequence: CLIC5 ENST00000185206.12 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.901

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=-0.82).
• BP6: Variant 6-46079532-T-C is Benign according to our data. Variant chr6-46079532-T-C is described in ClinVar as [Benign]. Clinvar id is 1285748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC5	NM_001114086.2	c.540+171A>G		intron_variant
CLIC5	NM_001370649.1	c.-55+49972A>G		intron_variant
CLIC5	NM_001370650.1	c.540+171A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000185206.12	c.540+171A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26396 AN: 152108 Hom.: 2571 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.174 AC: 26418 AN: 152226 Hom.: 2573 Cov.: 33 AF XY: 0.176 AC XY: 13113 AN XY: 74434

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.167

Alfa AF: 0.170 Hom.: 1135

Bravo AF: 0.168

Asia WGS AF: 0.345 AC: 1198 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9381423; hg19: chr6-46047269;