rs3134057

Variant names:

• chr8-118941229-A-G
• rs3134057
• NM_002546.4:c.31-7929T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-118941229-A-G
• chr8-118941229-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.31-7929T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,016 control chromosomes in the GnomAD database, including 14,013 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 0.42 (14013 hom., cov: 32)
• Consequence: TNFRSF11B NM_002546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF11B	NM_002546.4	c.31-7929T>C		intron_variant	Intron 1 of 4	ENST00000297350.9	NP_002537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF11B	ENST00000297350.9	c.31-7929T>C		intron_variant	Intron 1 of 4	1	NM_002546.4	ENSP00000297350.4
TNFRSF11B	ENST00000517352.1	n.31-7929T>C		intron_variant	Intron 1 of 4	1		ENSP00000427924.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64476 AN: 151898 Hom.: 13995 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.424 AC: 64530 AN: 152016 Hom.: 14013 Cov.: 32 AF XY: 0.427 AC XY: 31745 AN XY: 74304

African (AFR) AF: 0.509 AC: 21087 AN: 41466

American (AMR) AF: 0.356 AC: 5441 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2321 AN: 5176

South Asian (SAS) AF: 0.490 AC: 2362 AN: 4820

European-Finnish (FIN) AF: 0.419 AC: 4416 AN: 10550

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25909 AN: 67954

Other (OTH) AF: 0.442 AC: 931 AN: 2106

Alfa AF: 0.398 Hom.: 20506

Bravo AF: 0.422

Asia WGS AF: 0.477 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		1.0
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: rs3134057; hg19: chr8-119953468;