rs1033466

Positions:

• chr16-1471744-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001287.6(CLCN7):​c.141+3090C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,180 control chromosomes in the GnomAD database, including 9,767 homozygotes. 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 0.34 (9767 hom., cov: 33)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: CLCN7 NM_001287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN7	NM_001287.6	c.141+3090C>T		intron_variant		ENST00000382745.9	NP_001278.1
CLCN7	XM_011522354.2	c.-154C>T		5_prime_UTR_premature_start_codon_gain_variant	1/25		XP_011520656.1
CLCN7	XM_011522354.2	c.-154C>T		5_prime_UTR_variant	1/25		XP_011520656.1
CLCN7	NM_001114331.3	c.141+3090C>T		intron_variant			NP_001107803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN7	ENST00000382745.9	c.141+3090C>T		intron_variant		1	NM_001287.6	ENSP00000372193.4

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51462 AN: 152014 Hom.: 9742 Cov.: 33

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.188 AC: 9 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 3 AN XY: 30

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.339 AC: 51538 AN: 152132 Hom.: 9767 Cov.: 33 AF XY: 0.341 AC XY: 25395 AN XY: 74388

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.318

Alfa AF: 0.267 Hom.: 7686

Bravo AF: 0.347

Asia WGS AF: 0.464 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.84

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: rs1033466; hg19: chr16-1521745;