Genetic Variant TNFRSF10B:n.2648C>G (chr8-23020813-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000523752.5(TNFRSF10B):n.2648C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 454,124 control chromosomes in the GnomAD database, including 668 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 0.041 ( 182 hom., cov: 32)

Exomes 𝑓: 0.052 ( 486 hom. )

Consequence

TNFRSF10B
ENST00000523752.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.214

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5 link	c.*1858C>G	3_prime_UTR_variant	Exon 9 of 9	ENST00000276431.9	NP_003833.4	O14763-1Q7Z2I8
TNFRSF10B	NR_027140.2 link	n.3125C>G	non_coding_transcript_exon_variant	Exon 9 of 9
TNFRSF10B	NM_147187.3 link	c.*1858C>G	3_prime_UTR_variant	Exon 10 of 10		NP_671716.2	O14763-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000523752.5 link	n.2648C>G		non_coding_transcript_exon_variant	Exon 4 of 4	1
TNFRSF10B	ENST00000276431.9 link	c.*1858C>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_003842.5	ENSP00000276431.4		O14763-1

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6314

AN:

152204

Hom.:

181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0100

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0694

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0431

Gnomad FIN

AF:

0.0762

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0591

Gnomad OTH

AF:

0.0430

GnomAD2 exomes

AF:

0.0443

AC:

5781

AN:

130506

AF XY:

0.0464

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0224

Gnomad ASJ exome

AF:

0.0684

Gnomad EAS exome

AF:

0.0000959

Gnomad FIN exome

AF:

0.0708

Gnomad NFE exome

AF:

0.0602

Gnomad OTH exome

AF:

0.0539

GnomAD4 exome

AF:

0.0518

AC:

15648

AN:

301802

Hom.:

486

Cov.:

AF XY:

0.0520

AC XY:

8943

AN XY:

171998

show subpopulations

African (AFR)

AF:

0.0125

AC:

107

AN:

8554

American (AMR)

AF:

0.0227

AC:

620

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.0668

AC:

720

AN:

10786

East Asian (EAS)

AF:

0.00

AC:

AN:

9210

South Asian (SAS)

AF:

0.0472

AC:

2816

AN:

59650

European-Finnish (FIN)

AF:

0.0733

AC:

906

AN:

12366

Middle Eastern (MID)

AF:

0.0635

AC:

AN:

1150

European-Non Finnish (NFE)

AF:

0.0608

AC:

9660

AN:

158764

Other (OTH)

AF:

0.0531

AC:

746

AN:

14048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1572

3143

4715

6286

7858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.0415

AC:

6315

AN:

152322

Hom.:

182

Cov.:

AF XY:

0.0416

AC XY:

3100

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0100

AC:

416

AN:

41578

American (AMR)

AF:

0.0309

AC:

473

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0694

AC:

241

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0431

AC:

208

AN:

4826

European-Finnish (FIN)

AF:

0.0762

AC:

809

AN:

10616

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0591

AC:

4021

AN:

68010

Other (OTH)

AF:

0.0425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

311

622

933

1244

1555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0305

Hom.:

Bravo

AF:

0.0364

Asia WGS

AF:

0.0180

AC:

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

1.4

(source)

DANN

Benign

0.67

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over