6-45917324-G-T

Position:

• chr6-45917324-G-T

Variant summary

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

The NM_016929.5(CLIC5):​c.407-2915C>A 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 152,128 control chromosomes in the GnomAD database, including 1,247 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 0.11 (1247 hom., cov: 32)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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 (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIC5	NM_016929.5	c.407-2915C>A		intron_variant		ENST00000339561.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIC5	ENST00000339561.12	c.407-2915C>A		intron_variant		1	NM_016929.5	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16069 AN: 152010 Hom.: 1243 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0964

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0934

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

GnomAD4 genome AF: 0.106 AC: 16089 AN: 152128 Hom.: 1247 Cov.: 32 AF XY: 0.108 AC XY: 8023 AN XY: 74394

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0962

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.0981

Alfa AF: 0.0479 Hom.: 60

Bravo AF: 0.110

Asia WGS AF: 0.147 AC: 513 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	3.8
DANN	Benign	0.49

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: rs4714888; hg19: chr6-45885061;