rs12969154

Positions:

• chr18-62338910-G-A

Variant summary

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

The NM_003839.4(TNFRSF11A):​c.76-9258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 152,220 control chromosomes in the GnomAD database, including 799 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 0.069 (799 hom., cov: 32)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

Genes affected

TNFRSF11A (HGNC:11908): (TNF receptor superfamily member 11a) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptors can interact with various TRAF family proteins, through which this receptor induces the activation of NF-kappa B and MAPK8/JNK. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. This receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Paget disease of bone. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4	c.76-9258G>A		intron_variant		ENST00000586569.3	NP_003830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.76-9258G>A		intron_variant		1	NM_003839.4	ENSP00000465500	P2
TNFRSF11A	ENST00000269485.11	c.76-9258G>A		intron_variant		1		ENSP00000269485	A2

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10496 AN: 152102 Hom.: 799 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.00441

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0689 AC: 10487 AN: 152220 Hom.: 799 Cov.: 32 AF XY: 0.0758 AC XY: 5639 AN XY: 74440

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0567

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0629 Hom.: 397

Bravo AF: 0.0698

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
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: rs12969154; hg19: chr18-60006143;