rs1047266

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003842.5(TNFRSF10B):c.200C>T(p.Ala67Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,613,848 control chromosomes in the GnomAD database, including 6,251 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.069 ( 610 hom., cov: 32)

Exomes 𝑓: 0.076 ( 5641 hom. )

Consequence

TNFRSF10B
NM_003842.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.151

Publications

40 publications found

Variant links:

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

TNFRSF10B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005087942).

BP6

Variant 8-23043188-G-A is Benign according to our data. Variant chr8-23043188-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056241.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5 link	c.200C>T	p.Ala67Val	missense_variant	Exon 2 of 9	ENST00000276431.9	NP_003833.4	O14763-1Q7Z2I8
TNFRSF10B	NM_147187.3 link	c.200C>T	p.Ala67Val	missense_variant	Exon 2 of 10		NP_671716.2	O14763-2
TNFRSF10B	NR_027140.2 link	n.282-12316C>T		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9 link	c.200C>T	p.Ala67Val	missense_variant	Exon 2 of 9	1	NM_003842.5	ENSP00000276431.4		O14763-1

Frequencies

GnomAD3 genomes

AF:

0.0694

AC:

10547

AN:

152016

Hom.:

612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.0671

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.0402

Gnomad FIN

AF:

0.0822

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0712

Gnomad OTH

AF:

0.0722

GnomAD2 exomes

AF:

0.0967

AC:

24279

AN:

251018

AF XY:

0.0902

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.0670

Gnomad EAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.0816

Gnomad NFE exome

AF:

0.0699

Gnomad OTH exome

AF:

0.0846

GnomAD4 exome

AF:

0.0764

AC:

111663

AN:

1461714

Hom.:

5641

Cov.:

AF XY:

0.0748

AC XY:

54399

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.0116

AC:

390

AN:

33480

American (AMR)

AF:

0.180

AC:

8045

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0670

AC:

1750

AN:

26132

East Asian (EAS)

AF:

0.271

AC:

10742

AN:

39696

South Asian (SAS)

AF:

0.0386

AC:

3328

AN:

86246

European-Finnish (FIN)

AF:

0.0827

AC:

4418

AN:

53410

Middle Eastern (MID)

AF:

0.0189

AC:

109

AN:

5768

European-Non Finnish (NFE)

AF:

0.0700

AC:

77843

AN:

1111892

Other (OTH)

AF:

0.0834

AC:

5038

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

5214

10428

15643

20857

26071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3022

6044

9066

12088

15110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0693

AC:

10544

AN:

152134

Hom.:

610

Cov.:

AF XY:

0.0704

AC XY:

5237

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0166

AC:

689

AN:

41532

American (AMR)

AF:

0.130

AC:

1990

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0671

AC:

233

AN:

3470

East Asian (EAS)

AF:

0.290

AC:

1491

AN:

5138

South Asian (SAS)

AF:

0.0400

AC:

193

AN:

4820

European-Finnish (FIN)

AF:

0.0822

AC:

869

AN:

10572

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0712

AC:

4842

AN:

67998

Other (OTH)

AF:

0.0724

AC:

153

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

466

932

1399

1865

2331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0717

Hom.:

1800

Bravo

AF:

0.0751

TwinsUK

AF:

0.0609

AC:

226

ALSPAC

AF:

0.0672

AC:

259

ESP6500AA

AF:

0.0179

AC:

ESP6500EA

AF:

0.0699

AC:

601

ExAC

AF:

0.0904

AC:

10974

Asia WGS

AF:

0.141

AC:

489

AN:

3478

EpiCase

AF:

0.0678

EpiControl

AF:

0.0639

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TNFRSF10B-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.48

N;N

PhyloP100

-0.15

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.27

Sift

Benign

0.68

T;T

Sift4G

Benign

1.0

T;T

Polyphen

1.0

D;D

Vest4

0.061

MPC

0.065

ClinPred

0.015

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.083

gMVP

0.36

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over