rs3826619

chr18-62348517-G-Achr18-62348517-G-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.157+268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,144 control chromosomes in the GnomAD database, including 1,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1146 hom., cov: 32)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0810

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=-0.83).
• BP6: Variant 18-62348517-G-A is Benign according to our data. Variant chr18-62348517-G-A is described in ClinVar as [Benign]. Clinvar id is 1263481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11A	NM_003839.4	c.157+268G>A		intron_variant		ENST00000586569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.157+268G>A		intron_variant		1	NM_003839.4	P2
TNFRSF11A	ENST00000269485.11	c.157+268G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15732 AN: 152026 Hom.: 1145 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.103 AC: 15740 AN: 152144 Hom.: 1146 Cov.: 32 AF XY: 0.111 AC XY: 8246 AN XY: 74368

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0635 Hom.: 88

Bravo AF: 0.0938

Asia WGS AF: 0.237 AC: 821 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.7
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: rs3826619; hg19: chr18-60015750;