8-23037252-T-C

Variant names:

• chr8-23037252-T-C
• rs12541497
• NM_003842.5:c.250+5886A>G

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+5886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,890 control chromosomes in the GnomAD database, including 7,544 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 0.31 (7544 hom., cov: 31)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.250+5886A>G		intron_variant	Intron 2 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.250+5886A>G		intron_variant	Intron 2 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.282-6380A>G		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.250+5886A>G		intron_variant	Intron 2 of 8	1	NM_003842.5	ENSP00000276431.4
TNFRSF10B	ENST00000347739.3	c.250+5886A>G		intron_variant	Intron 2 of 9	1		ENSP00000317859.3
TNFRSF10B	ENST00000519910.1	n.257+5886A>G		intron_variant	Intron 2 of 4	4
TNFRSF10B	ENST00000523504.5	n.145-6380A>G		intron_variant	Intron 1 of 8	2		ENSP00000427999.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47290 AN: 151772 Hom.: 7543 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.311 AC: 47311 AN: 151890 Hom.: 7544 Cov.: 31 AF XY: 0.312 AC XY: 23154 AN XY: 74238

African (AFR) AF: 0.246 AC: 10189 AN: 41406

American (AMR) AF: 0.353 AC: 5395 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1846 AN: 5138

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4816

European-Finnish (FIN) AF: 0.324 AC: 3425 AN: 10562

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.338 AC: 22961 AN: 67924

Other (OTH) AF: 0.312 AC: 657 AN: 2106

Alfa AF: 0.320 Hom.: 2762

Bravo AF: 0.311

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.74
PhyloP100		0.27
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: rs12541497; hg19: chr8-22894765;