rs6469788

Variant names:

• chr8-118940511-A-C
• rs6469788
• NM_002546.4:c.31-7211T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-118940511-A-C
• chr8-118940511-A-G
• chr8-118940511-A-T

Variant summary

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

The NM_002546.4(TNFRSF11B):​c.31-7211T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,978 control chromosomes in the GnomAD database, including 36,069 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 0.67 (36069 hom., cov: 31)
• Consequence: TNFRSF11B NM_002546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 8 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 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.31-7211T>G		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.31-7211T>G		intron	N/A	ENSP00000297350.4	O00300
	TNFRSF11B	ENST00000517352.1	TSL:1	n.31-7211T>G		intron	N/A	ENSP00000427924.1	E5RFV7
	TNFRSF11B	ENST00000966249.1		c.31-3716T>G		intron	N/A	ENSP00000636308.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101622 AN: 151860 Hom.: 36006 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.669 AC: 101736 AN: 151978 Hom.: 36069 Cov.: 31 AF XY: 0.671 AC XY: 49827 AN XY: 74276

African (AFR) AF: 0.916 AC: 37989 AN: 41482

American (AMR) AF: 0.606 AC: 9250 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2332 AN: 3472

East Asian (EAS) AF: 0.751 AC: 3882 AN: 5168

South Asian (SAS) AF: 0.670 AC: 3223 AN: 4814

European-Finnish (FIN) AF: 0.559 AC: 5894 AN: 10544

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37234 AN: 67934

Other (OTH) AF: 0.660 AC: 1391 AN: 2106

Alfa AF: 0.614 Hom.: 3736

Bravo AF: 0.679

Asia WGS AF: 0.761 AC: 2646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.48
PhyloP100		-1.6
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: rs6469788; hg19: chr8-119952750;