chr16-1448950-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001287.6(CLCN7):​c.1797+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CLCN7
NM_001287.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.254

Publications

10 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLCN7NM_001287.6 linkc.1797+16G>C intron_variant Intron 19 of 24 ENST00000382745.9 NP_001278.1 P51798-1
CLCN7NM_001114331.3 linkc.1725+16G>C intron_variant Intron 18 of 23 NP_001107803.1 P51798-2
CLCN7XM_011522354.2 linkc.1623+16G>C intron_variant Intron 19 of 24 XP_011520656.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLCN7ENST00000382745.9 linkc.1797+16G>C intron_variant Intron 19 of 24 1 NM_001287.6 ENSP00000372193.4 P51798-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152094
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459586
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
726116
show subpopulations
African (AFR)
AF:
0.0000597
AC:
2
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51250
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111918
Other (OTH)
AF:
0.00
AC:
0
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000657
AC:
1
AN:
152094
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74300
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41408
American (AMR)
AF:
0.00
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67990
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
996

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.088
DANN
Benign
0.44
PhyloP100
-0.25

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

Other links and lift over

dbSNP: rs12932780; hg19: chr16-1498951; API