chr18-62370567-G-T

Position:

• chr18-62370567-G-T

Variant summary

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

The NM_003839.4(TNFRSF11A):​c.1567+1083G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,992 control chromosomes in the GnomAD database, including 7,195 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 0.30 (7195 hom., cov: 32)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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 (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4	c.1567+1083G>T		intron_variant		ENST00000586569.3	NP_003830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.1567+1083G>T		intron_variant		1	NM_003839.4	ENSP00000465500	P2
TNFRSF11A	ENST00000269485.11	c.616+10518G>T		intron_variant		1		ENSP00000269485	A2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45130 AN: 151874 Hom.: 7182 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.297 AC: 45194 AN: 151992 Hom.: 7195 Cov.: 32 AF XY: 0.290 AC XY: 21522 AN XY: 74276

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.310

Alfa AF: 0.308 Hom.: 1550

Bravo AF: 0.302

Asia WGS AF: 0.111 AC: 390 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	0.67
DANN	Benign	0.49

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: rs6567274; hg19: chr18-60037800;