6-45917961-C-T

Position:

• chr6-45917961-C-T

Variant summary

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

The NM_016929.5(CLIC5):​c.407-3552G>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 152,270 control chromosomes in the GnomAD database, including 1,113 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 (1113 hom., cov: 33)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.407-3552G>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.407-3552G>A		intron_variant		1	NM_016929.5	ENSP00000344165	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16094 AN: 152152 Hom.: 1113 Cov.: 33

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.106 AC: 16092 AN: 152270 Hom.: 1113 Cov.: 33 AF XY: 0.103 AC XY: 7684 AN XY: 74446

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0454

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.107

Alfa AF: 0.136 Hom.: 563

Bravo AF: 0.0997

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.58

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: rs11758298; hg19: chr6-45885698;