chr18-62325314-G-A

Variant names:

Variant summary

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

The NM_003839.4(TNFRSF11A):c.-39G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 964,284 control chromosomes in the GnomAD database, including 34,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 5996 hom., cov: 31)

Exomes 𝑓: 0.26 ( 28259 hom. )

Consequence

TNFRSF11A
NM_003839.4 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.25

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=-0.56).

BP6

Variant 18-62325314-G-A is Benign according to our data. Variant chr18-62325314-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4 link	c.-39G>A		5_prime_UTR_variant	Exon 1 of 10	ENST00000586569.3	NP_003830.1	Q9Y6Q6-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNFRSF11A	ENST00000586569 link	c.-39G>A	5_prime_UTR_variant	Exon 1 of 10	1	NM_003839.4	ENSP00000465500.1	Q9Y6Q6-1
TNFRSF11A	ENST00000269485 link	c.-39G>A	5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000269485.7	Q9Y6Q6-2
TNFRSF11A	ENST00000592013.1 link	n.-12G>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

40719

AN:

146588

Hom.:

5994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.275

GnomAD3 exomes

AF:

0.0645

AC:

371

AN:

5752

Hom.:

AF XY:

0.0636

AC XY:

202

AN XY:

3178

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.0435

Gnomad ASJ exome

AF:

0.0594

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0396

Gnomad FIN exome

AF:

0.0679

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.0479

GnomAD4 exome

AF:

0.259

AC:

211770

AN:

817590

Hom.:

28259

Cov.:

AF XY:

0.258

AC XY:

98727

AN XY:

382418

show subpopulations

Gnomad4 AFR exome

AF:

0.334

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.0824

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.238

GnomAD4 genome

AF:

0.278

AC:

40733

AN:

146694

Hom.:

5996

Cov.:

AF XY:

0.273

AC XY:

19490

AN XY:

71404

show subpopulations

Gnomad4 AFR

AF:

0.343

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.285

Hom.:

773

Bravo

AF:

0.274

Asia WGS

AF:

0.171

AC:

485

AN:

2834

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bone Paget disease

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteopetrosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

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