8-118933902-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002546.4(TNFRSF11B):c.31-602A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,226 control chromosomes in the GnomAD database, including 61,114 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 0.89 (61114 hom., cov: 32)
• Consequence: TNFRSF11B NM_002546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.86

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11B	NM_002546.4	c.31-602A>G		intron_variant		ENST00000297350.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF11B	ENST00000297350.9	c.31-602A>G		intron_variant		1	NM_002546.4	P1
TNFRSF11B	ENST00000517352.1	c.31-602A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136128 AN: 152108 Hom.: 61072 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.895 AC: 136224 AN: 152226 Hom.: 61114 Cov.: 32 AF XY: 0.893 AC XY: 66436 AN XY: 74408

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.914

Alfa AF: 0.909 Hom.: 7807

Bravo AF: 0.889

Asia WGS AF: 0.809 AC: 2816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.039
Dann	Benign	0.45

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: rs3134053; hg19: chr8-119946141;