Variant chr18-62359938-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.522-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,607,418 control chromosomes in the GnomAD database, including 221,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24553 hom., cov: 32)

Exomes 𝑓: 0.52 ( 197258 hom. )

Consequence

TNFRSF11A
NM_003839.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0790

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 18-62359938-C-T is Benign according to our data. Variant chr18-62359938-C-T is described in ClinVar as [Benign]. Clinvar id is 259180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-62359938-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11A	NM_003839.4 linkuse as main transcript	c.522-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000586569.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
TNFRSF11A	ENST00000586569.3 linkuse as main transcript	c.522-17C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_003839.4	P2	Q9Y6Q6-1
TNFRSF11A	ENST00000269485.11 linkuse as main transcript	c.522-17C>T	splice_polypyrimidine_tract_variant, intron_variant	1		A2	Q9Y6Q6-2
TNFRSF11A	ENST00000587697.1 linkuse as main transcript	n.440-17C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85624

AN:

151878

Hom.:

24508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.691

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.600

GnomAD3 exomes

AF:

0.545

AC:

137045

AN:

251422

Hom.:

38578

AF XY:

0.532

AC XY:

72228

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.647

Gnomad AMR exome

AF:

0.664

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.699

Gnomad SAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.532

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.544

GnomAD4 exome

AF:

0.517

AC:

752139

AN:

1455422

Hom.:

197258

Cov.:

AF XY:

0.512

AC XY:

371081

AN XY:

724410

show subpopulations

Gnomad4 AFR exome

AF:

0.643

Gnomad4 AMR exome

AF:

0.664

Gnomad4 ASJ exome

AF:

0.544

Gnomad4 EAS exome

AF:

0.687

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.532

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.529

GnomAD4 genome

AF:

0.564

AC:

85731

AN:

151996

Hom.:

24553

Cov.:

AF XY:

0.565

AC XY:

41969

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.640

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.691

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.529

Gnomad4 NFE

AF:

0.511

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.527

Hom.:

36801

Bravo

AF:

0.581

Asia WGS

AF:

0.569

AC:

1979

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.4

DANN

Benign

0.44

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