rs3777580

Variant names:

• chr6-45942727-A-C
• rs3777580
• NM_016929.5:c.300-1074T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-45942727-A-C
• chr6-45942727-A-G
• chr6-45942727-A-T

Variant summary

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

The NM_016929.5(CLIC5):​c.300-1074T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,122 control chromosomes in the GnomAD database, including 18,406 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 0.46 (18406 hom., cov: 33)
• Consequence: CLIC5 NM_016929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 2 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

LOC124901326 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016929.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	NM_016929.5	MANE Select	c.300-1074T>G		intron	N/A	NP_058625.2
	CLIC5	NM_001114086.2		c.777-1074T>G		intron	N/A	NP_001107558.1
	CLIC5	NM_001370650.1		c.777-1074T>G		intron	N/A	NP_001357579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	ENST00000339561.12	TSL:1 MANE Select	c.300-1074T>G		intron	N/A	ENSP00000344165.6
	CLIC5	ENST00000185206.12	TSL:1	c.777-1074T>G		intron	N/A	ENSP00000185206.6
	CLIC5	ENST00000644324.1		c.300-1074T>G		intron	N/A	ENSP00000495186.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70593 AN: 152004 Hom.: 18381 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.465 AC: 70674 AN: 152122 Hom.: 18406 Cov.: 33 AF XY: 0.466 AC XY: 34631 AN XY: 74362

African (AFR) AF: 0.689 AC: 28572 AN: 41468

American (AMR) AF: 0.390 AC: 5965 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3470

East Asian (EAS) AF: 0.668 AC: 3458 AN: 5176

South Asian (SAS) AF: 0.567 AC: 2736 AN: 4822

European-Finnish (FIN) AF: 0.313 AC: 3314 AN: 10584

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23977 AN: 67984

Other (OTH) AF: 0.455 AC: 961 AN: 2114

Alfa AF: 0.400 Hom.: 33278

Bravo AF: 0.478

Asia WGS AF: 0.631 AC: 2193 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.17
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: rs3777580; hg19: chr6-45910464;