chr6-45951982-A-G

Variant names:

• chr6-45951982-A-G
• rs3777587
• NM_016929.5:c.174-2601T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016929.5(CLIC5):​c.174-2601T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,248 control chromosomes in the GnomAD database, including 58,732 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 0.87 (58732 hom., cov: 33)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 1 publications found

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]

CLIC5 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 103

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302748 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIC5	NM_016929.5	c.174-2601T>C		intron_variant	Intron 2 of 5	ENST00000339561.12	NP_058625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIC5	ENST00000339561.12	c.174-2601T>C		intron_variant	Intron 2 of 5	1	NM_016929.5	ENSP00000344165.6

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133079 AN: 152130 Hom.: 58684 Cov.: 33

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.875 AC: 133186 AN: 152248 Hom.: 58732 Cov.: 33 AF XY: 0.869 AC XY: 64713 AN XY: 74440

African (AFR) AF: 0.895 AC: 37192 AN: 41542

American (AMR) AF: 0.845 AC: 12921 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3129 AN: 3472

East Asian (EAS) AF: 0.491 AC: 2541 AN: 5174

South Asian (SAS) AF: 0.798 AC: 3847 AN: 4822

European-Finnish (FIN) AF: 0.882 AC: 9363 AN: 10610

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61221 AN: 68028

Other (OTH) AF: 0.871 AC: 1836 AN: 2108

Alfa AF: 0.894 Hom.: 12681

Bravo AF: 0.873

Asia WGS AF: 0.682 AC: 2374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3777587; hg19: chr6-45919719;