rs72871427

Variant names:

• chr6-45912436-A-G
• rs72871427
• NM_016929.5:c.588+1792T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256023.2(CLIC5):​c.*274T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,174,364 control chromosomes in the GnomAD database, including 473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (79 hom., cov: 33)
  • Exomes 𝑓: 0.026 (394 hom.)
• Consequence: CLIC5 NM_001256023.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.78
• Publications: 0 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-45912436-A-G is Benign according to our data. Variant chr6-45912436-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1316401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256023.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	NM_016929.5	MANE Select	c.588+1792T>C		intron	N/A	NP_058625.2	Q53G01
	CLIC5	NM_001256023.2		c.*274T>C		3_prime_UTR	Exon 6 of 6	NP_001242952.1	Q9NZA1-3
	CLIC5	NM_001114086.2		c.1065+1792T>C		intron	N/A	NP_001107558.1	Q9NZA1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIC5	ENST00000339561.12	TSL:1 MANE Select	c.588+1792T>C		intron	N/A	ENSP00000344165.6	Q9NZA1-2
	CLIC5	ENST00000185206.12	TSL:1	c.1065+1792T>C		intron	N/A	ENSP00000185206.6	Q9NZA1-1
	CLIC5	ENST00000544153.3	TSL:2	c.*274T>C		3_prime_UTR	Exon 6 of 6	ENSP00000439195.1	Q9NZA1-3

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4670 AN: 152186 Hom.: 78 Cov.: 33

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0262 AC: 26729 AN: 1022060 Hom.: 394 Cov.: 32 AF XY: 0.0261 AC XY: 12663 AN XY: 484742

African (AFR) AF: 0.0473 AC: 1054 AN: 22300

American (AMR) AF: 0.0559 AC: 661 AN: 11834

Ashkenazi Jewish (ASJ) AF: 0.00914 AC: 96 AN: 10504

East Asian (EAS) AF: 0.00324 AC: 51 AN: 15726

South Asian (SAS) AF: 0.0244 AC: 1012 AN: 41548

European-Finnish (FIN) AF: 0.0177 AC: 156 AN: 8806

Middle Eastern (MID) AF: 0.0167 AC: 40 AN: 2392

European-Non Finnish (NFE) AF: 0.0261 AC: 22785 AN: 871372

Other (OTH) AF: 0.0233 AC: 874 AN: 37578

GnomAD4 genome AF: 0.0308 AC: 4692 AN: 152304 Hom.: 79 Cov.: 33 AF XY: 0.0307 AC XY: 2287 AN XY: 74468

African (AFR) AF: 0.0452 AC: 1877 AN: 41560

American (AMR) AF: 0.0382 AC: 585 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5174

South Asian (SAS) AF: 0.0215 AC: 104 AN: 4828

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0266 AC: 1812 AN: 68024

Other (OTH) AF: 0.0260 AC: 55 AN: 2114

Alfa AF: 0.0355 Hom.: 75

Bravo AF: 0.0337

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.42
PhyloP100		-2.8
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: rs72871427; hg19: chr6-45880173;