rs4263037

Positions:

• chr18-62349000-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.157+751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,862 control chromosomes in the GnomAD database, including 28,708 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 0.61 (28708 hom., cov: 30)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11A	NM_003839.4	c.157+751G>A		intron_variant		ENST00000586569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.157+751G>A		intron_variant		1	NM_003839.4	P2
TNFRSF11A	ENST00000269485.11	c.157+751G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93026 AN: 151744 Hom.: 28660 Cov.: 30

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.613 AC: 93138 AN: 151862 Hom.: 28708 Cov.: 30 AF XY: 0.617 AC XY: 45760 AN XY: 74198

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.606

Alfa AF: 0.614 Hom.: 37839

Bravo AF: 0.604

Asia WGS AF: 0.628 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.73
DANN	Benign	0.59

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: rs4263037; hg19: chr18-60016233;