Variant rs7050330 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001289.6(CLIC2):c.57+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,192,179 control chromosomes in the GnomAD database, including 73 homozygotes. There are 864 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 39 hom., 422 hem., cov: 22)

Exomes 𝑓: 0.0016 ( 34 hom. 442 hem. )

Consequence

CLIC2
NM_001289.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.267

Variant links:

Genes affected

CLIC2 (HGNC:2063): (chloride intracellular channel 2) This gene encodes a chloride intracellular channel protein. Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. This protein plays a role in inhibiting the function of ryanodine receptor 2. A mutation in this gene is the cause of an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]

CLIC2 links:

CLIC2 (HGNC:):

CLIC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant X-155334361-G-A is Benign according to our data. Variant chrX-155334361-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 446044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIC2	NM_001289.6 linkuse as main transcript	c.57+10C>T		intron_variant		ENST00000369449.7	NP_001280.3	O15247

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CLIC2	ENST00000369449.7 linkuse as main transcript	c.57+10C>T	intron_variant	1	NM_001289.6	ENSP00000358460.2	O15247
CLIC2	ENST00000321926.4 linkuse as main transcript	c.57+10C>T	intron_variant	3		ENSP00000318558.4	A6PVS0
CLIC2	ENST00000465553.5 linkuse as main transcript	n.172+10C>T	intron_variant	3
CLIC2	ENST00000491205.1 linkuse as main transcript	n.57+10C>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

1546

AN:

111889

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

422

AN XY:

34175

show subpopulations

Gnomad AFR

AF:

0.0480

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000367

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.0112

GnomAD3 exomes

AF:

0.00410

AC:

742

AN:

181095

Hom.:

AF XY:

0.00285

AC XY:

191

AN XY:

67041

show subpopulations

Gnomad AFR exome

AF:

0.0491

Gnomad AMR exome

AF:

0.00274

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00159

AC:

1716

AN:

1080236

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

442

AN XY:

348280

show subpopulations

Gnomad4 AFR exome

AF:

0.0536

Gnomad4 AMR exome

AF:

0.00285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000968

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.0138

AC:

1548

AN:

111943

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

422

AN XY:

34239

show subpopulations

Gnomad4 AFR

AF:

0.0480

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000368

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.0111

Alfa

AF:

0.00440

Hom.:

Bravo

AF:

0.0160

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 19, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.3

DANN

Benign

0.88

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over