chr8-23034761-T-C

Variant names:

• chr8-23034761-T-C
• rs11785599
• NM_003842.5:c.251-3889A>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.251-3889A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,184 control chromosomes in the GnomAD database, including 14,200 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 0.40 (14200 hom., cov: 33)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• 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 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.251-3889A>G		intron_variant	Intron 2 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.251-3889A>G		intron_variant	Intron 2 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.282-3889A>G		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.251-3889A>G		intron_variant	Intron 2 of 8	1	NM_003842.5	ENSP00000276431.4
TNFRSF10B	ENST00000347739.3	c.251-3889A>G		intron_variant	Intron 2 of 9	1		ENSP00000317859.3
TNFRSF10B	ENST00000519910.1	n.258-3889A>G		intron_variant	Intron 2 of 4	4
TNFRSF10B	ENST00000523504.5	n.145-3889A>G		intron_variant	Intron 1 of 8	2		ENSP00000427999.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61400 AN: 152066 Hom.: 14196 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.404 AC: 61426 AN: 152184 Hom.: 14200 Cov.: 33 AF XY: 0.406 AC XY: 30169 AN XY: 74396

African (AFR) AF: 0.167 AC: 6941 AN: 41540

American (AMR) AF: 0.413 AC: 6317 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3466

East Asian (EAS) AF: 0.432 AC: 2229 AN: 5164

South Asian (SAS) AF: 0.367 AC: 1769 AN: 4822

European-Finnish (FIN) AF: 0.567 AC: 6004 AN: 10586

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34649 AN: 67992

Other (OTH) AF: 0.413 AC: 874 AN: 2116

Alfa AF: 0.474 Hom.: 32109

Bravo AF: 0.384

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.43
PhyloP100		0.055
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: rs11785599; hg19: chr8-22892274;