rs3081400

Variant names:

• chr8-118935561-ACTTTC-A
• rs3081400
• NM_002546.4:c.31-2266_31-2262delGAAAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002546.4(TNFRSF11B):​c.31-2266_31-2262delGAAAG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11561 hom., cov: 0)
• Consequence: TNFRSF11B NM_002546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 5 publications found

Genes affected

TNFRSF11B (HGNC:11909): (TNF receptor superfamily member 11b) The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is an osteoblast-secreted decoy receptor that functions as a negative regulator of bone resorption. This protein specifically binds to its ligand, osteoprotegerin ligand, both of which are key extracellular regulators of osteoclast development. Studies of the mouse counterpart also suggest that this protein and its ligand play a role in lymph-node organogenesis and vascular calcification. Alternatively spliced transcript variants of this gene have been reported, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

TNFRSF11B Gene-Disease associations (from GenCC):

• juvenile Paget disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002546.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF11B	NM_002546.4	MANE Select	c.31-2266_31-2262delGAAAG		intron	N/A	NP_002537.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF11B	ENST00000297350.9	TSL:1 MANE Select	c.31-2266_31-2262delGAAAG		intron	N/A	ENSP00000297350.4
	TNFRSF11B	ENST00000517352.1	TSL:1	n.31-2266_31-2262delGAAAG		intron	N/A	ENSP00000427924.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57615 AN: 151532 Hom.: 11547 Cov.: 0

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.380 AC: 57640 AN: 151650 Hom.: 11561 Cov.: 0 AF XY: 0.376 AC XY: 27875 AN XY: 74118

African (AFR) AF: 0.257 AC: 10619 AN: 41366

American (AMR) AF: 0.412 AC: 6280 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3462

East Asian (EAS) AF: 0.247 AC: 1274 AN: 5152

South Asian (SAS) AF: 0.330 AC: 1586 AN: 4804

European-Finnish (FIN) AF: 0.441 AC: 4628 AN: 10502

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30652 AN: 67810

Other (OTH) AF: 0.378 AC: 796 AN: 2104

Alfa AF: 0.416 Hom.: 1678

Bravo AF: 0.378

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3081400; hg19: chr8-119947800;