8-118948422-C-G

Position:

• chr8-118948422-C-G

Variant summary

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

The NM_002546.4(TNFRSF11B):​c.30+3370G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,042 control chromosomes in the GnomAD database, including 36,179 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 (36179 hom., cov: 31)
• Consequence: TNFRSF11B NM_002546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11B	NM_002546.4	c.30+3370G>C		intron_variant		ENST00000297350.9	NP_002537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF11B	ENST00000297350.9	c.30+3370G>C		intron_variant		1	NM_002546.4	ENSP00000297350.4
TNFRSF11B	ENST00000517352.1	n.30+3370G>C		intron_variant		1		ENSP00000427924.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101750 AN: 151924 Hom.: 36116 Cov.: 31

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.558

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: 0.670 AC: 101864 AN: 152042 Hom.: 36179 Cov.: 31 AF XY: 0.671 AC XY: 49888 AN XY: 74310

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.661

Alfa AF: 0.441 Hom.: 1096

Bravo AF: 0.679

Asia WGS AF: 0.760 AC: 2643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.56

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: rs6469789; hg19: chr8-119960661;