dbSNP rs7050330: CLIC2:c.57+10C>T (chrX-155334361-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome
Inheritance: XL, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

CLIC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289.6. 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
	CLIC2	NM_001289.6	MANE Select	c.57+10C>T		intron	N/A	NP_001280.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLIC2	ENST00000369449.7	TSL:1 MANE Select	c.57+10C>T	intron	N/A	ENSP00000358460.2	O15247
CLIC2	ENST00000948941.1		c.57+10C>T	intron	N/A	ENSP00000619000.1
CLIC2	ENST00000321926.4	TSL:3	c.57+10C>T	intron	N/A	ENSP00000318558.4	A6PVS0

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

1546

AN:

111889

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00410

AC:

742

AN:

181095

AF XY:

0.00285

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 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

African (AFR)

AF:

0.0536

AC:

1396

AN:

26030

American (AMR)

AF:

0.00285

AC:

100

AN:

35101

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19226

East Asian (EAS)

AF:

0.00

AC:

AN:

30140

South Asian (SAS)

AF:

0.000186

AC:

AN:

53728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40520

Middle Eastern (MID)

AF:

0.00202

AC:

AN:

3953

European-Non Finnish (NFE)

AF:

0.0000968

AC:

AN:

826095

Other (OTH)

AF:

0.00268

AC:

122

AN:

45443

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0138

AC:

1548

AN:

111943

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

422

AN XY:

34239

show subpopulations

African (AFR)

AF:

0.0480

AC:

1481

AN:

30863

American (AMR)

AF:

0.00379

AC:

AN:

10554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3515

South Asian (SAS)

AF:

0.000368

AC:

AN:

2718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6128

Middle Eastern (MID)

AF:

0.00463

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000151

AC:

AN:

53097

Other (OTH)

AF:

0.0111

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

100

150

200

250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00421

Hom.:

Bravo

AF:

0.0160

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.3

(source)

DANN

Benign

0.88

PhyloP100

0.27

PromoterAI

0.030

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over