rs10090860

Variant names:

• chr8-23040572-C-T
• rs10090860
• NM_003842.5:c.250+2566G>A

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.250+2566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 149,038 control chromosomes in the GnomAD database, including 9,080 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 0.34 (9080 hom., cov: 29)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 0 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 Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	NM_003842.5	MANE Select	c.250+2566G>A		intron	N/A	NP_003833.4
	TNFRSF10B	NM_147187.3		c.250+2566G>A		intron	N/A	NP_671716.2
	TNFRSF10B	NR_027140.2		n.282-9700G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.250+2566G>A		intron	N/A	ENSP00000276431.4
	TNFRSF10B	ENST00000347739.3	TSL:1	c.250+2566G>A		intron	N/A	ENSP00000317859.3
	TNFRSF10B	ENST00000519910.1	TSL:4	n.257+2566G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.342 AC: 50975 AN: 148944 Hom.: 9060 Cov.: 29

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.342 AC: 51037 AN: 149038 Hom.: 9080 Cov.: 29 AF XY: 0.340 AC XY: 24689 AN XY: 72572

African (AFR) AF: 0.404 AC: 16362 AN: 40500

American (AMR) AF: 0.336 AC: 5005 AN: 14876

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1004 AN: 3462

East Asian (EAS) AF: 0.161 AC: 825 AN: 5128

South Asian (SAS) AF: 0.139 AC: 664 AN: 4764

European-Finnish (FIN) AF: 0.370 AC: 3530 AN: 9530

Middle Eastern (MID) AF: 0.365 AC: 103 AN: 282

European-Non Finnish (NFE) AF: 0.334 AC: 22555 AN: 67532

Other (OTH) AF: 0.341 AC: 702 AN: 2056

Alfa AF: 0.212 Hom.: 468

Bravo AF: 0.346

Asia WGS AF: 0.170 AC: 589 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.040
DANN	Benign	0.35
PhyloP100		-1.5
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: rs10090860; hg19: chr8-22898085;