rs17069895

Positions:

• chr18-62361625-C-T

Variant summary

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

The NM_003839.4(TNFRSF11A):​c.617-55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,514,404 control chromosomes in the GnomAD database, including 637 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 0.0091 (79 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (558 hom.)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4	c.617-55C>T		intron_variant		ENST00000586569.3	NP_003830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.617-55C>T		intron_variant		1	NM_003839.4	ENSP00000465500.1
TNFRSF11A	ENST00000269485.11	c.616+1576C>T		intron_variant		1		ENSP00000269485.7

Frequencies

GnomAD3 genomes AF: 0.00915 AC: 1393 AN: 152168 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.00443

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.00765

GnomAD4 exome AF: 0.00670 AC: 9120 AN: 1362118 Hom.: 558 AF XY: 0.00635 AC XY: 4340 AN XY: 683586

Gnomad4 AFR exome AF: 0.000574

Gnomad4 AMR exome AF: 0.0339

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.00439

Gnomad4 FIN exome AF: 0.00329

Gnomad4 NFE exome AF: 0.000486

Gnomad4 OTH exome AF: 0.00760

GnomAD4 genome AF: 0.00911 AC: 1388 AN: 152286 Hom.: 79 Cov.: 32 AF XY: 0.0104 AC XY: 772 AN XY: 74446

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.00443

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00499 Hom.: 1

Bravo AF: 0.0120

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.75

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: rs17069895; hg19: chr18-60028858; COSMIC: COSV54022082; COSMIC: COSV54022082;