rs3729618

Variant names:

• chr6-45920336-A-G
• rs3729618
• NM_016929.5:c.407-5927T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-45920336-A-G
• chr6-45920336-A-T

Variant summary

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

The NM_016929.5(CLIC5):​c.407-5927T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 943,144 control chromosomes in the GnomAD database, including 43,737 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 0.27 (5932 hom., cov: 32)
  • Exomes 𝑓: 0.30 (37805 hom.)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.407-5927T>C		intron_variant	Intron 4 of 5	ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12	c.407-5927T>C		intron_variant	Intron 4 of 5	1	NM_016929.5	ENSP00000344165.6

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41202 AN: 151990 Hom.: 5931 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.301 AC: 238426 AN: 791036 Hom.: 37805 Cov.: 15 AF XY: 0.303 AC XY: 110735 AN XY: 365728

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.271 AC: 41211 AN: 152108 Hom.: 5932 Cov.: 32 AF XY: 0.271 AC XY: 20180 AN XY: 74354

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.284

Alfa AF: 0.272 Hom.: 954

Bravo AF: 0.262

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3729618; hg19: chr6-45888073;