rs3081400

Positions:

• chr8-118935561-ACTTTC-A

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11B	NM_002546.4	c.31-2266_31-2262delGAAAG		intron_variant		ENST00000297350.9	NP_002537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF11B	ENST00000297350.9	c.31-2266_31-2262delGAAAG		intron_variant		1	NM_002546.4	ENSP00000297350.4
TNFRSF11B	ENST00000517352.1	n.31-2266_31-2262delGAAAG		intron_variant		1		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

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.378

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 v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3081400; hg19: chr8-119947800;