8-118952044-G-T

Variant names:

• chr8-118952044-G-T
• rs2073617
• NM_002546.4:c.-223C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002546.4(TNFRSF11B):​c.-223C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFRSF11B NM_002546.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 141 publications found

Genes affected

TNFRSF11B (HGNC:11909): (TNF receptor superfamily member 11b) The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is an osteoblast-secreted decoy receptor that functions as a negative regulator of bone resorption. This protein specifically binds to its ligand, osteoprotegerin ligand, both of which are key extracellular regulators of osteoclast development. Studies of the mouse counterpart also suggest that this protein and its ligand play a role in lymph-node organogenesis and vascular calcification. Alternatively spliced transcript variants of this gene have been reported, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

COLEC10 (HGNC:2220): (collectin subfamily member 10) This gene encodes a member of the C-lectin family, proteins that possess collagen-like sequences and carbohydrate recognition domains. The other members of this family are secreted proteins and bind to carbohydrate antigens on microorganisms facilitating their recognition and removal. This gene product is a cytosolic protein, a characteristic that suggests that it may have different biological functions than other C-lectins. [provided by RefSeq, Jul 2008]

COLEC10 Gene-Disease associations (from GenCC):

• 3MC syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: G2P
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002546.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF11B	NM_002546.4	MANE Select	c.-223C>A		upstream_gene	N/A	NP_002537.3
	COLEC10	NM_001324095.2		c.-658G>T		upstream_gene	N/A	NP_001311024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF11B	ENST00000297350.9	TSL:1 MANE Select	c.-223C>A		upstream_gene	N/A	ENSP00000297350.4
	TNFRSF11B	ENST00000517352.1	TSL:1	n.-223C>A		upstream_gene	N/A	ENSP00000427924.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 414068 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 219292

African (AFR) AF: 0.00 AC: 0 AN: 11632

American (AMR) AF: 0.00 AC: 0 AN: 19034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12732

East Asian (EAS) AF: 0.00 AC: 0 AN: 28226

South Asian (SAS) AF: 0.00 AC: 0 AN: 44936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2874

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 245950

Other (OTH) AF: 0.00 AC: 0 AN: 23658

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.63
PhyloP100		-0.096
PromoterAI		-0.11	Neutral

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

Other links and lift over

dbSNP: rs2073617; hg19: chr8-119964283;