rs35021217

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001287.6(CLCN7):c.2073+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,553,366 control chromosomes in the GnomAD database, including 7,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 453 hom., cov: 33)

Exomes 𝑓: 0.094 ( 7016 hom. )

Consequence

CLCN7
NM_001287.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.60

Publications

8 publications found

Variant links:

Genes affected

CLCN7 (HGNC:2025): (chloride voltage-gated channel 7) The product of this gene belongs to the CLC chloride channel family of proteins. Chloride channels play important roles in the plasma membrane and in intracellular organelles. This gene encodes chloride channel 7. Defects in this gene are the cause of osteopetrosis autosomal recessive type 4 (OPTB4), also called infantile malignant osteopetrosis type 2 as well as the cause of autosomal dominant osteopetrosis type 2 (OPTA2), also called autosomal dominant Albers-Schonberg disease or marble disease autosoml dominant. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. [provided by RefSeq, Jul 2008]

CLCN7 Gene-Disease associations (from GenCC):

autosomal dominant osteopetrosis 2
Inheritance: AD, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
autosomal recessive osteopetrosis 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Genomics England PanelApp, Ambry Genetics
hypopigmentation, organomegaly, and delayed myelination and development
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
autosomal recessive osteopetrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive osteopetrosis 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CLCN7 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=-0.91).

BP6

Variant 16-1447639-G-A is Benign according to our data. Variant chr16-1447639-G-A is described in ClinVar as Benign. ClinVar VariationId is 257955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLCN7	NM_001287.6 link	c.2073+16C>T	intron_variant	Intron 22 of 24	ENST00000382745.9	NP_001278.1	P51798-1
CLCN7	NM_001114331.3 link	c.2001+16C>T	intron_variant	Intron 21 of 23		NP_001107803.1	P51798-2
CLCN7	XM_011522354.2 link	c.1899+16C>T	intron_variant	Intron 22 of 24		XP_011520656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCN7	ENST00000382745.9 link	c.2073+16C>T		intron_variant	Intron 22 of 24	1	NM_001287.6	ENSP00000372193.4		P51798-1

Frequencies

GnomAD3 genomes

AF:

0.0685

AC:

10424

AN:

152154

Hom.:

453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0775

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0342

Gnomad FIN

AF:

0.0483

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0783

GnomAD2 exomes

AF:

0.0647

AC:

10028

AN:

154990

AF XY:

0.0646

show subpopulations

Gnomad AFR exome

AF:

0.0256

Gnomad AMR exome

AF:

0.0508

Gnomad ASJ exome

AF:

0.0846

Gnomad EAS exome

AF:

0.000174

Gnomad FIN exome

AF:

0.0511

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.0835

GnomAD4 exome

AF:

0.0943

AC:

132104

AN:

1401094

Hom.:

7016

Cov.:

AF XY:

0.0924

AC XY:

63870

AN XY:

691446

show subpopulations

African (AFR)

AF:

0.0266

AC:

845

AN:

31730

American (AMR)

AF:

0.0557

AC:

2014

AN:

36152

Ashkenazi Jewish (ASJ)

AF:

0.0874

AC:

2202

AN:

25194

East Asian (EAS)

AF:

0.000195

AC:

AN:

35988

South Asian (SAS)

AF:

0.0323

AC:

2567

AN:

79452

European-Finnish (FIN)

AF:

0.0567

AC:

2725

AN:

48026

Middle Eastern (MID)

AF:

0.0816

AC:

465

AN:

5698

European-Non Finnish (NFE)

AF:

0.107

AC:

115964

AN:

1080764

Other (OTH)

AF:

0.0915

AC:

5315

AN:

58090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

7757

15514

23272

31029

38786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4280

8560

12840

17120

21400

<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:

0.0684

AC:

10419

AN:

152272

Hom.:

453

Cov.:

AF XY:

0.0638

AC XY:

4752

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0284

AC:

1181

AN:

41574

American (AMR)

AF:

0.0773

AC:

1184

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0847

AC:

294

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.0353

AC:

170

AN:

4820

European-Finnish (FIN)

AF:

0.0483

AC:

513

AN:

10614

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6826

AN:

67992

Other (OTH)

AF:

0.0766

AC:

162

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

519

1038

1557

2076

2595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0869

Hom.:

146

Bravo

AF:

0.0707

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.019

(source)

DANN

Benign

0.61

PhyloP100

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over