chr18-62350973-A-T

Position:

• chr18-62350973-A-T

Variant summary

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

The ENST00000586569.3(TNFRSF11A):​c.283+1036A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 147,294 control chromosomes in the GnomAD database, including 30,033 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 0.64 (30033 hom., cov: 26)
• Consequence: TNFRSF11A ENST00000586569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF11A	NM_003839.4	c.283+1036A>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.283+1036A>T		intron_variant		1	NM_003839.4	ENSP00000465500	P2
TNFRSF11A	ENST00000269485.11	c.283+1036A>T		intron_variant		1		ENSP00000269485	A2

Frequencies

GnomAD3 genomes AF: 0.642 AC: 94499 AN: 147190 Hom.: 29985 Cov.: 26

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.493

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.642 AC: 94603 AN: 147294 Hom.: 30033 Cov.: 26 AF XY: 0.644 AC XY: 46126 AN XY: 71588

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.625

Alfa AF: 0.648 Hom.: 4031

Bravo AF: 0.630

Asia WGS AF: 0.624 AC: 2163 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.72

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: rs11664594; hg19: chr18-60018206;