rs10866818

Variant names:

• chr8-23030894-G-A
• rs10866818
• NM_003842.5:c.251-22C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-23030894-G-A
• chr8-23030894-G-C
• chr8-23030894-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003842.5(TNFRSF10B):​c.251-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 1,561,402 control chromosomes in the GnomAD database, including 617,074 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 0.85 (55898 hom., cov: 29)
  • Exomes 𝑓: 0.89 (561176 hom.)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 11 publications found

Genes affected

TNFRSF10B (HGNC:11905): (TNF receptor superfamily member 10b) The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces an apoptosis signal. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for this gene. [provided by RefSeq, Mar 2009]

TNFRSF10B Gene-Disease associations (from GenCC):

• head and neck squamous cell carcinoma

  Inheritance: Unknown, AD, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003842.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	NM_003842.5	MANE Select	c.251-22C>T		intron	N/A	NP_003833.4
	TNFRSF10B	NM_147187.3		c.251-22C>T		intron	N/A	NP_671716.2	O14763-2
	TNFRSF10B	NR_027140.2		n.282-22C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.251-22C>T		intron	N/A	ENSP00000276431.4	O14763-1
	TNFRSF10B	ENST00000347739.3	TSL:1	c.251-22C>T		intron	N/A	ENSP00000317859.3	O14763-2
	TNFRSF10B	ENST00000931215.1		c.251-22C>T		intron	N/A	ENSP00000601274.1

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129692 AN: 151814 Hom.: 55862 Cov.: 29

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.850

GnomAD2 exomes AF: 0.890 AC: 198571 AN: 223048 AF XY: 0.891

Gnomad AFR exome AF: 0.741

Gnomad AMR exome AF: 0.884

Gnomad ASJ exome AF: 0.905

Gnomad EAS exome AF: 0.979

Gnomad FIN exome AF: 0.935

Gnomad NFE exome AF: 0.897

Gnomad OTH exome AF: 0.885

GnomAD4 exome AF: 0.892 AC: 1256712 AN: 1409472 Hom.: 561176 Cov.: 21 AF XY: 0.891 AC XY: 625407 AN XY: 701658

African (AFR) AF: 0.730 AC: 23744 AN: 32530

American (AMR) AF: 0.881 AC: 36508 AN: 41456

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 23056 AN: 25392

East Asian (EAS) AF: 0.975 AC: 38090 AN: 39068

South Asian (SAS) AF: 0.858 AC: 71058 AN: 82788

European-Finnish (FIN) AF: 0.934 AC: 48320 AN: 51754

Middle Eastern (MID) AF: 0.879 AC: 3735 AN: 4248

European-Non Finnish (NFE) AF: 0.895 AC: 960494 AN: 1073738

Other (OTH) AF: 0.884 AC: 51707 AN: 58498

GnomAD4 genome AF: 0.854 AC: 129788 AN: 151930 Hom.: 55898 Cov.: 29 AF XY: 0.857 AC XY: 63697 AN XY: 74284

African (AFR) AF: 0.740 AC: 30596 AN: 41358

American (AMR) AF: 0.869 AC: 13265 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3123 AN: 3470

East Asian (EAS) AF: 0.981 AC: 5047 AN: 5146

South Asian (SAS) AF: 0.857 AC: 4121 AN: 4810

European-Finnish (FIN) AF: 0.935 AC: 9899 AN: 10582

Middle Eastern (MID) AF: 0.860 AC: 251 AN: 292

European-Non Finnish (NFE) AF: 0.895 AC: 60859 AN: 67992

Other (OTH) AF: 0.851 AC: 1795 AN: 2110

Alfa AF: 0.884 Hom.: 39415

Bravo AF: 0.844

Asia WGS AF: 0.911 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.75
PhyloP100		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10866818; hg19: chr8-22888407;