rs6567270

Positions:

• chr18-62359772-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003839.4(TNFRSF11A):​c.522-183T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,026 control chromosomes in the GnomAD database, including 18,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.49 (18779 hom., cov: 32)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0870

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 18-62359772-T-A is Benign according to our data. Variant chr18-62359772-T-A is described in ClinVar as [Benign]. Clinvar id is 1253093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11A	NM_003839.4	c.522-183T>A		intron_variant		ENST00000586569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.522-183T>A		intron_variant		1	NM_003839.4	P2
TNFRSF11A	ENST00000269485.11	c.522-183T>A		intron_variant		1		A2
TNFRSF11A	ENST00000587697.1	n.440-183T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75123 AN: 151908 Hom.: 18757 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.495 AC: 75189 AN: 152026 Hom.: 18779 Cov.: 32 AF XY: 0.493 AC XY: 36671 AN XY: 74322

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.529

Alfa AF: 0.502 Hom.: 2407

Bravo AF: 0.499

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.41

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: rs6567270; hg19: chr18-60027005; COSMIC: COSV54022353;