rs8094884

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003839.4(TNFRSF11A):​c.617-785G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,000 control chromosomes in the GnomAD database, including 13,358 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 0.41 ( 13358 hom., cov: 31)

Consequence

TNFRSF11A
NM_003839.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.47
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNFRSF11ANM_003839.4 linkuse as main transcriptc.617-785G>A intron_variant ENST00000586569.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNFRSF11AENST00000586569.3 linkuse as main transcriptc.617-785G>A intron_variant 1 NM_003839.4 P2Q9Y6Q6-1
TNFRSF11AENST00000269485.11 linkuse as main transcriptc.616+846G>A intron_variant 1 A2Q9Y6Q6-2

Frequencies

GnomAD3 genomes
AF:
0.410
AC:
62253
AN:
151882
Hom.:
13358
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.376
Gnomad AMI
AF:
0.471
Gnomad AMR
AF:
0.429
Gnomad ASJ
AF:
0.511
Gnomad EAS
AF:
0.108
Gnomad SAS
AF:
0.278
Gnomad FIN
AF:
0.369
Gnomad MID
AF:
0.579
Gnomad NFE
AF:
0.457
Gnomad OTH
AF:
0.449
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.410
AC:
62270
AN:
152000
Hom.:
13358
Cov.:
31
AF XY:
0.402
AC XY:
29875
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.375
Gnomad4 AMR
AF:
0.429
Gnomad4 ASJ
AF:
0.511
Gnomad4 EAS
AF:
0.108
Gnomad4 SAS
AF:
0.279
Gnomad4 FIN
AF:
0.369
Gnomad4 NFE
AF:
0.457
Gnomad4 OTH
AF:
0.446
Alfa
AF:
0.455
Hom.:
21826
Bravo
AF:
0.419
Asia WGS
AF:
0.221
AC:
775
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
8.5
DANN
Benign
0.79

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8094884; hg19: chr18-60028128; API