rs12458117

Positions:

• chr18-62360215-G-A
• chr18-62360215-G-T

Variant summary

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

The ENST00000586569.3(TNFRSF11A):​c.616+166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,030 control chromosomes in the GnomAD database, including 1,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1346 hom., cov: 32)
• Consequence: TNFRSF11A ENST00000586569.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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=-0.91).
• BP6: Variant 18-62360215-G-A is Benign according to our data. Variant chr18-62360215-G-A is described in ClinVar as [Benign]. Clinvar id is 1220751.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4	c.616+166G>A		intron_variant		ENST00000586569.3	NP_003830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.616+166G>A		intron_variant		1	NM_003839.4	ENSP00000465500	P2
TNFRSF11A	ENST00000269485.11	c.616+166G>A		intron_variant		1		ENSP00000269485	A2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18124 AN: 151914 Hom.: 1343 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.119 AC: 18139 AN: 152030 Hom.: 1346 Cov.: 32 AF XY: 0.125 AC XY: 9305 AN XY: 74332

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0982 Hom.: 292

Bravo AF: 0.113

Asia WGS AF: 0.216 AC: 748 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	-0.91
CADD	Benign	0.22
DANN	Benign	0.80

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: rs12458117; hg19: chr18-60027448;