rs3102727

Variant names:

• chr8-118943710-C-T
• rs3102727
• NM_002546.4:c.30+8082G>A

Variant summary

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

The NM_002546.4(TNFRSF11B):​c.30+8082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 152,138 control chromosomes in the GnomAD database, including 76 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 0.013 (76 hom., cov: 32)
• Consequence: TNFRSF11B NM_002546.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF11B	NM_002546.4	c.30+8082G>A		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.30+8082G>A		intron_variant	Intron 1 of 4	1	NM_002546.4	ENSP00000297350.4
TNFRSF11B	ENST00000517352.1	n.30+8082G>A		intron_variant	Intron 1 of 4	1		ENSP00000427924.1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1926 AN: 152020 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0712

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00925

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.0127 AC: 1928 AN: 152138 Hom.: 76 Cov.: 32 AF XY: 0.0150 AC XY: 1113 AN XY: 74380

African (AFR) AF: 0.00246 AC: 102 AN: 41508

American (AMR) AF: 0.0716 AC: 1094 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3466

East Asian (EAS) AF: 0.0907 AC: 468 AN: 5162

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4816

European-Finnish (FIN) AF: 0.00925 AC: 98 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00172 AC: 117 AN: 67986

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00635 Hom.: 2

Bravo AF: 0.0169

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.6
DANN	Benign	0.51
PhyloP100		0.14
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: rs3102727; hg19: chr8-119955949;