rs4436867

Positions:

• chr18-62336411-C-A
• chr18-62336411-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.75+10984C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,202 control chromosomes in the GnomAD database, including 2,380 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 0.15 (2379 hom., cov: 32)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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 (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11A	NM_003839.4	c.75+10984C>A		intron_variant		ENST00000586569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.75+10984C>A		intron_variant		1	NM_003839.4	P2
TNFRSF11A	ENST00000269485.11	c.75+10984C>A		intron_variant		1		A2
TNFRSF11A	ENST00000592013.1	n.200C>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23073 AN: 152048 Hom.: 2379 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.250 AC: 9 AN: 36 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 8 AN XY: 32

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.152 AC: 23081 AN: 152166 Hom.: 2379 Cov.: 32 AF XY: 0.150 AC XY: 11139 AN XY: 74362

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0643 Hom.: 100

Bravo AF: 0.142

Asia WGS AF: 0.0670 AC: 235 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	1.6
DANN	Benign	0.45

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: rs4436867; hg19: chr18-60003644;