rs3756804

Positions:

• chr6-46129040-T-C

Variant summary

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

The NM_001370650.1(CLIC5):​c.-46+464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,262 control chromosomes in the GnomAD database, including 830 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 0.097 (830 hom., cov: 32)
• Consequence: CLIC5 NM_001370650.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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]

ENSG00000231769 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC5	NM_001370650.1	c.-46+464A>G		intron_variant			NP_001357579.1
CLIC5	NM_001370649.1	c.-55+464A>G		intron_variant			NP_001357578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000231769	ENST00000437249.2	n.117+550A>G		intron_variant		3
ENSG00000231769	ENST00000444038.3	n.328+464A>G		intron_variant		3
ENSG00000231769	ENST00000669498.1	n.354+464A>G		intron_variant
ENSG00000231769	ENST00000689613.2	n.260+550A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14712 AN: 152144 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0967 AC: 14724 AN: 152262 Hom.: 830 Cov.: 32 AF XY: 0.0996 AC XY: 7417 AN XY: 74462

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0700 Hom.: 742

Bravo AF: 0.0950

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.4
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3756804; hg19: chr6-46096777;