rs6600147

Variant names:

• chr16-1457987-C-T
• rs6600147
• NM_001287.6:c.676-231G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-1457987-C-T
• chr16-1457987-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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: Ambry Genetics, ClinGen, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal recessive osteopetrosis 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• hypopigmentation, organomegaly, and delayed myelination and development

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• autosomal recessive osteopetrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive osteopetrosis 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN7	NM_001287.6	MANE Select	c.676-231G>A		intron	N/A	NP_001278.1	P51798-1
	CLCN7	NM_001114331.3		c.604-231G>A		intron	N/A	NP_001107803.1	P51798-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN7	ENST00000382745.9	TSL:1 MANE Select	c.676-231G>A		intron	N/A	ENSP00000372193.4	P51798-1
	CLCN7	ENST00000262318.12	TSL:5	c.604-231G>A		intron	N/A	ENSP00000262318.8	H0Y2M6
	CLCN7	ENST00000892994.1		c.757-231G>A		intron	N/A	ENSP00000563053.1

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

African (AFR) AF: 0.491 AC: 20363 AN: 41496

American (AMR) AF: 0.587 AC: 8984 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3468

East Asian (EAS) AF: 0.849 AC: 4377 AN: 5158

South Asian (SAS) AF: 0.481 AC: 2321 AN: 4830

European-Finnish (FIN) AF: 0.711 AC: 7536 AN: 10598

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40439 AN: 67912

Other (OTH) AF: 0.581 AC: 1222 AN: 2102

Alfa AF: 0.583 Hom.: 35875

Bravo AF: 0.571

Asia WGS AF: 0.613 AC: 2128 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.43
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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