NM_003842.5:c.144+11373T>C

Variant names:

• chr8-23057378-A-G
• rs10095594
• NM_003842.5:c.144+11373T>C

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.144+11373T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 149,138 control chromosomes in the GnomAD database, including 34,305 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 0.67 (34305 hom., cov: 27)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 5 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.144+11373T>C		intron_variant	Intron 1 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.144+11373T>C		intron_variant	Intron 1 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.281+11373T>C		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.144+11373T>C		intron_variant	Intron 1 of 8	1	NM_003842.5	ENSP00000276431.4
TNFRSF10B	ENST00000347739.3	c.144+11373T>C		intron_variant	Intron 1 of 9	1		ENSP00000317859.3
TNFRSF10B	ENST00000519028.1	n.272+11373T>C		intron_variant	Intron 1 of 1	2
TNFRSF10B	ENST00000523504.5	n.144+11373T>C		intron_variant	Intron 1 of 8	2		ENSP00000427999.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 100433 AN: 149030 Hom.: 34274 Cov.: 27

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.603

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.674 AC: 100518 AN: 149138 Hom.: 34305 Cov.: 27 AF XY: 0.677 AC XY: 49148 AN XY: 72574

African (AFR) AF: 0.660 AC: 26437 AN: 40026

American (AMR) AF: 0.662 AC: 9970 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2305 AN: 3460

East Asian (EAS) AF: 0.899 AC: 4593 AN: 5108

South Asian (SAS) AF: 0.675 AC: 3219 AN: 4768

European-Finnish (FIN) AF: 0.735 AC: 7146 AN: 9728

Middle Eastern (MID) AF: 0.617 AC: 179 AN: 290

European-Non Finnish (NFE) AF: 0.661 AC: 44772 AN: 67722

Other (OTH) AF: 0.653 AC: 1352 AN: 2072

Alfa AF: 0.658 Hom.: 54968

Bravo AF: 0.666

Asia WGS AF: 0.785 AC: 2725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.7
DANN	Benign	0.25
PhyloP100		-1.3
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: rs10095594; hg19: chr8-22914891;