rs3134062

Variant names:

• chr8-118947039-A-G
• rs3134062
• NM_002546.4:c.30+4753T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002546.4(TNFRSF11B):​c.30+4753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 152,232 control chromosomes in the GnomAD database, including 397 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 0.068 (397 hom., cov: 32)
• Consequence: TNFRSF11B NM_002546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF11B	NM_002546.4	MANE Select	c.30+4753T>C		intron	N/A	NP_002537.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF11B	ENST00000297350.9	TSL:1 MANE Select	c.30+4753T>C		intron	N/A	ENSP00000297350.4
	TNFRSF11B	ENST00000517352.1	TSL:1	n.30+4753T>C		intron	N/A	ENSP00000427924.1
	TNFRSF11B	ENST00000966249.1		c.30+4753T>C		intron	N/A	ENSP00000636308.1

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10359 AN: 152114 Hom.: 395 Cov.: 32

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0558

Gnomad OTH AF: 0.0527

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

GnomAD4 genome AF: 0.0681 AC: 10366 AN: 152232 Hom.: 397 Cov.: 32 AF XY: 0.0682 AC XY: 5078 AN XY: 74446

African (AFR) AF: 0.0784 AC: 3257 AN: 41526

American (AMR) AF: 0.112 AC: 1712 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3468

East Asian (EAS) AF: 0.127 AC: 656 AN: 5170

South Asian (SAS) AF: 0.0375 AC: 181 AN: 4824

European-Finnish (FIN) AF: 0.0386 AC: 410 AN: 10626

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0558 AC: 3796 AN: 68014

Other (OTH) AF: 0.0517 AC: 109 AN: 2108

Alfa AF: 0.0577 Hom.: 142

Bravo AF: 0.0742

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.70
PhyloP100		-0.022
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: rs3134062; hg19: chr8-119959278;