rs4242387

Variant names:

• chr8-23040039-A-G
• rs4242387
• NM_003842.5:c.250+3099T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-23040039-A-G
• chr8-23040039-A-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.250+3099T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,372 control chromosomes in the GnomAD database, including 25,738 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 0.55 (25738 hom., cov: 29)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.250+3099T>C		intron_variant	Intron 2 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.250+3099T>C		intron_variant	Intron 2 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.282-9167T>C		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.250+3099T>C		intron_variant	Intron 2 of 8	1	NM_003842.5	ENSP00000276431.4
TNFRSF10B	ENST00000347739.3	c.250+3099T>C		intron_variant	Intron 2 of 9	1		ENSP00000317859.3
TNFRSF10B	ENST00000519910.1	n.257+3099T>C		intron_variant	Intron 2 of 4	4
TNFRSF10B	ENST00000523504.5	n.145-9167T>C		intron_variant	Intron 1 of 8	2		ENSP00000427999.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83204 AN: 151256 Hom.: 25738 Cov.: 29

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.550 AC: 83209 AN: 151372 Hom.: 25738 Cov.: 29 AF XY: 0.552 AC XY: 40800 AN XY: 73928

African (AFR) AF: 0.247 AC: 10178 AN: 41156

American (AMR) AF: 0.572 AC: 8693 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2403 AN: 3464

East Asian (EAS) AF: 0.756 AC: 3890 AN: 5144

South Asian (SAS) AF: 0.574 AC: 2764 AN: 4812

European-Finnish (FIN) AF: 0.696 AC: 7239 AN: 10402

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46101 AN: 67934

Other (OTH) AF: 0.571 AC: 1186 AN: 2076

Alfa AF: 0.582 Hom.: 4281

Bravo AF: 0.530

Asia WGS AF: 0.600 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.60
PhyloP100		0.31
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: rs4242387; hg19: chr8-22897552;