rs7233197

Positions:

• chr18-62330201-T-C

Variant summary

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

The NM_003839.4(TNFRSF11A):​c.75+4774T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,270 control chromosomes in the GnomAD database, including 64,857 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 0.92 (64857 hom., cov: 32)
• Consequence: TNFRSF11A NM_003839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF11A	NM_003839.4	c.75+4774T>C		intron_variant		ENST00000586569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF11A	ENST00000586569.3	c.75+4774T>C		intron_variant		1	NM_003839.4	P2
TNFRSF11A	ENST00000269485.11	c.75+4774T>C		intron_variant		1		A2
TNFRSF11A	ENST00000592013.1	n.102+4774T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140287 AN: 152152 Hom.: 64798 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.922 AC: 140404 AN: 152270 Hom.: 64857 Cov.: 32 AF XY: 0.922 AC XY: 68630 AN XY: 74426

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.918

Alfa AF: 0.908 Hom.: 60823

Bravo AF: 0.928

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.45

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: rs7233197; hg19: chr18-59997434;