Variant chr18-62384708-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003839.4(TNFRSF11A):c.1568-43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,598,578 control chromosomes in the GnomAD database, including 51,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3348 hom., cov: 29)

Exomes 𝑓: 0.24 ( 47929 hom. )

Consequence

TNFRSF11A
NM_003839.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.142

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]

TNFRSF11A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 18-62384708-C-T is Benign according to our data. Variant chr18-62384708-C-T is described in ClinVar as [Benign]. Clinvar id is 259179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4 link	c.1568-43C>T		intron_variant		ENST00000586569.3	NP_003830.1	Q9Y6Q6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF11A	ENST00000586569.3 link	c.1568-43C>T		intron_variant		1	NM_003839.4	ENSP00000465500.1		Q9Y6Q6-1
TNFRSF11A	ENST00000269485.11 link	c.617-43C>T		intron_variant		1		ENSP00000269485.7		Q9Y6Q6-2

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27396

AN:

151560

Hom.:

3345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.00274

Gnomad SAS

AF:

0.0677

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.180

AC:

40995

AN:

227680

Hom.:

4734

AF XY:

0.183

AC XY:

22481

AN XY:

122782

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.000564

Gnomad SAS exome

AF:

0.0772

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.245

AC:

353933

AN:

1446898

Hom.:

47929

Cov.:

AF XY:

0.240

AC XY:

172690

AN XY:

718120

show subpopulations

Gnomad4 AFR exome

AF:

0.0394

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.253

Gnomad4 EAS exome

AF:

0.000584

Gnomad4 SAS exome

AF:

0.0805

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.181

AC:

27403

AN:

151680

Hom.:

3348

Cov.:

AF XY:

0.173

AC XY:

12818

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.0498

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.261

Gnomad4 EAS

AF:

0.00275

Gnomad4 SAS

AF:

0.0679

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.161

Hom.:

468

Bravo

AF:

0.177

Asia WGS

AF:

0.0820

AC:

288

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.90

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over