rs2235580

chr16-1465161-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001287.6(CLCN7):c.213+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,082,180 control chromosomes in the GnomAD database, including 107,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13649 hom., cov: 33)
  • Exomes 𝑓: 0.45 (94007 hom.)
• Consequence: CLCN7 NM_001287.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.857

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-1465161-C-T is Benign according to our data. Variant chr16-1465161-C-T is described in ClinVar as [Benign]. Clinvar id is 1283737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN7	NM_001287.6	c.213+106G>A		intron_variant		ENST00000382745.9
CLCN7	NM_001114331.3	c.142-3487G>A		intron_variant
CLCN7	XM_011522354.2	c.39+106G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN7	ENST00000382745.9	c.213+106G>A		intron_variant		1	NM_001287.6	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62788 AN: 151968 Hom.: 13648 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.446 AC: 414927 AN: 930094 Hom.: 94007 AF XY: 0.447 AC XY: 213853 AN XY: 478474

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.413 AC: 62808 AN: 152086 Hom.: 13649 Cov.: 33 AF XY: 0.415 AC XY: 30816 AN XY: 74342

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.427

Alfa AF: 0.463 Hom.: 6689

Bravo AF: 0.400

Asia WGS AF: 0.351 AC: 1224 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.47
Dann	Benign	0.42

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

Other links and lift over

dbSNP: rs2235580; hg19: chr16-1515162;