chr18-62339745-C-G

Position:

• chr18-62339745-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003839.4(TNFRSF11A):​c.76-8423C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,966 control chromosomes in the GnomAD database, including 23,844 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (23844 hom., cov: 32)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4	c.76-8423C>G		intron_variant		ENST00000586569.3	NP_003830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.76-8423C>G		intron_variant		1	NM_003839.4	ENSP00000465500	P2
TNFRSF11A	ENST00000269485.11	c.76-8423C>G		intron_variant		1		ENSP00000269485	A2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85024 AN: 151848 Hom.: 23818 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.560 AC: 85095 AN: 151966 Hom.: 23844 Cov.: 32 AF XY: 0.562 AC XY: 41730 AN XY: 74262

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.558

Alfa AF: 0.563 Hom.: 3069

Bravo AF: 0.561

Asia WGS AF: 0.625 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.025
DANN	Benign	0.42

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: rs8086340; hg19: chr18-60006978;