chr8-23027596-A-G

Variant names:

• chr8-23027596-A-G
• rs1105944
• NM_003842.5:c.780+126T>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.780+126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,348,246 control chromosomes in the GnomAD database, including 537,304 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 0.86 (56932 hom., cov: 31)
  • Exomes 𝑓: 0.90 (480372 hom.)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.780+126T>C		intron_variant	Intron 6 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.693+126T>C		intron_variant	Intron 7 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.724+126T>C		intron_variant	Intron 6 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.780+126T>C		intron_variant	Intron 6 of 8	1	NM_003842.5	ENSP00000276431.4

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131128 AN: 152050 Hom.: 56897 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.857

GnomAD4 exome AF: 0.896 AC: 1071133 AN: 1196078 Hom.: 480372 Cov.: 15 AF XY: 0.895 AC XY: 540632 AN XY: 603934

African (AFR) AF: 0.757 AC: 21067 AN: 27828

American (AMR) AF: 0.883 AC: 34546 AN: 39126

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 20955 AN: 22932

East Asian (EAS) AF: 0.975 AC: 36450 AN: 37398

South Asian (SAS) AF: 0.867 AC: 67178 AN: 77474

European-Finnish (FIN) AF: 0.934 AC: 41382 AN: 44310

Middle Eastern (MID) AF: 0.884 AC: 4648 AN: 5260

European-Non Finnish (NFE) AF: 0.898 AC: 799022 AN: 890046

Other (OTH) AF: 0.887 AC: 45885 AN: 51704

GnomAD4 genome AF: 0.862 AC: 131227 AN: 152168 Hom.: 56932 Cov.: 31 AF XY: 0.866 AC XY: 64399 AN XY: 74406

African (AFR) AF: 0.764 AC: 31713 AN: 41496

American (AMR) AF: 0.873 AC: 13363 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3147 AN: 3472

East Asian (EAS) AF: 0.981 AC: 5068 AN: 5168

South Asian (SAS) AF: 0.864 AC: 4172 AN: 4830

European-Finnish (FIN) AF: 0.936 AC: 9930 AN: 10612

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60941 AN: 67978

Other (OTH) AF: 0.858 AC: 1807 AN: 2106

Alfa AF: 0.880 Hom.: 7324

Bravo AF: 0.854

Asia WGS AF: 0.917 AC: 3187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.8
DANN	Benign	0.87
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1105944; hg19: chr8-22885109;