rs7050330

Variant summary

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

The ENST00000369449.7(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
ENST00000369449.7 intron

Scores

2

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]

Genome browser will be placed here

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
CLIC2NM_001289.6 linkuse as main transcriptc.57+10C>T intron_variant ENST00000369449.7 NP_001280.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CLIC2ENST00000369449.7 linkuse as main transcriptc.57+10C>T intron_variant 1 NM_001289.6 ENSP00000358460 P1
CLIC2ENST00000321926.4 linkuse as main transcriptc.57+10C>T intron_variant 3 ENSP00000318558
CLIC2ENST00000465553.5 linkuse as main transcriptn.172+10C>T intron_variant, non_coding_transcript_variant 3
CLIC2ENST00000491205.1 linkuse as main transcriptn.57+10C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0138
AC:
1546
AN:
111889
Hom.:
39
Cov.:
22
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.:
29
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.:
34
Cov.:
27
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.:
39
Cov.:
22
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.:
50
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsApr 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.

Other links and lift over

dbSNP: rs7050330; hg19: chrX-154563670; API