rs7231887

chr18-62364256-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.731-2452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 152,206 control chromosomes in the GnomAD database, including 770 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 0.095 (770 hom., cov: 32)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11A	NM_003839.4	c.731-2452G>A		intron_variant		ENST00000586569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.731-2452G>A		intron_variant		1	NM_003839.4	P2
TNFRSF11A	ENST00000269485.11	c.616+4207G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14508 AN: 152088 Hom.: 771 Cov.: 32

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0954 AC: 14513 AN: 152206 Hom.: 770 Cov.: 32 AF XY: 0.0984 AC XY: 7324 AN XY: 74434

Gnomad4 AFR AF: 0.0449

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.106

Alfa AF: 0.104 Hom.: 384

Bravo AF: 0.0929

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.0
Dann	Benign	0.74

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: rs7231887; hg19: chr18-60031489;