16-1457987-C-T

Position:

• chr16-1457987-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.676-231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,060 control chromosomes in the GnomAD database, including 26,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (26008 hom., cov: 34)
• Consequence: CLCN7 NM_001287.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

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=-1.0).
• BP6: Variant 16-1457987-C-T is Benign according to our data. Variant chr16-1457987-C-T is described in ClinVar as [Benign]. Clinvar id is 1283731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN7	NM_001287.6	c.676-231G>A		intron_variant		ENST00000382745.9
CLCN7	NM_001114331.3	c.604-231G>A		intron_variant
CLCN7	XM_011522354.2	c.502-231G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN7	ENST00000382745.9	c.676-231G>A		intron_variant		1	NM_001287.6	P1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87912 AN: 151942 Hom.: 26004 Cov.: 34

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.586

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.578 AC: 87952 AN: 152060 Hom.: 26008 Cov.: 34 AF XY: 0.580 AC XY: 43102 AN XY: 74344

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.581

Alfa AF: 0.585 Hom.: 27977

Bravo AF: 0.571

Asia WGS AF: 0.613 AC: 2128 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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.43

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: rs6600147; hg19: chr16-1507988; COSMIC: COSV51972606; COSMIC: COSV51972606;