chr18-62330406-G-A

Position:

• chr18-62330406-G-A

Variant summary

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

The NM_003839.4(TNFRSF11A):​c.75+4979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 152,270 control chromosomes in the GnomAD database, including 120 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 0.029 (120 hom., cov: 32)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4	c.75+4979G>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.75+4979G>A		intron_variant		1	NM_003839.4	ENSP00000465500	P2
TNFRSF11A	ENST00000269485.11	c.75+4979G>A		intron_variant		1		ENSP00000269485	A2
TNFRSF11A	ENST00000592013.1	n.102+4979G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4357 AN: 152152 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0287 AC: 4367 AN: 152270 Hom.: 120 Cov.: 32 AF XY: 0.0319 AC XY: 2373 AN XY: 74444

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0168 Hom.: 11

Bravo AF: 0.0240

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.82

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: rs9956850; hg19: chr18-59997639;