rs8083511

Positions:

• chr18-62361422-A-C
• chr18-62361422-A-G
• chr18-62361422-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003839.4(TNFRSF11A):​c.617-258A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,952 control chromosomes in the GnomAD database, including 5,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5915 hom., cov: 31)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.152

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 18-62361422-A-C is Benign according to our data. Variant chr18-62361422-A-C is described in ClinVar as [Benign]. Clinvar id is 1278941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11A	NM_003839.4	c.617-258A>C		intron_variant		ENST00000586569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.617-258A>C		intron_variant		1	NM_003839.4	P2
TNFRSF11A	ENST00000269485.11	c.616+1373A>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39636 AN: 151834 Hom.: 5907 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.261 AC: 39683 AN: 151952 Hom.: 5915 Cov.: 31 AF XY: 0.264 AC XY: 19621 AN XY: 74308

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.266

Alfa AF: 0.195 Hom.: 4105

Bravo AF: 0.274

Asia WGS AF: 0.338 AC: 1176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.66

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: rs8083511; hg19: chr18-60028655;