8-23068839-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003842.5(TNFRSF10B):c.56G>A(p.Gly19Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,262 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 18 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 20 hom. )

Consequence

TNFRSF10B
NM_003842.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0250

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 links:

ENSG00000246130 (HGNC:27809):

ENSG00000246130 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004155576).

BP6

Variant 8-23068839-C-T is Benign according to our data. Variant chr8-23068839-C-T is described in ClinVar as [Benign]. Clinvar id is 714378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00693 (1056/152328) while in subpopulation AFR AF= 0.0246 (1023/41576). AF 95% confidence interval is 0.0234. There are 18 homozygotes in gnomad4. There are 509 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1056 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5 link	c.56G>A	p.Gly19Asp	missense_variant	Exon 1 of 9	ENST00000276431.9	NP_003833.4	O14763-1Q7Z2I8
TNFRSF10B	NM_147187.3 link	c.56G>A	p.Gly19Asp	missense_variant	Exon 1 of 10		NP_671716.2	O14763-2
TNFRSF10B	NR_027140.2 link	n.193G>A		non_coding_transcript_exon_variant	Exon 1 of 9
TNFRSF10B-AS1	NR_038873.1 link	n.192+419C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9 link	c.56G>A	p.Gly19Asp	missense_variant	Exon 1 of 9	1	NM_003842.5	ENSP00000276431.4		O14763-1

Frequencies

GnomAD3 genomes

AF:

0.00689

AC:

1049

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00176

AC:

433

AN:

245908

Hom.:

AF XY:

0.00132

AC XY:

177

AN XY:

134366

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.000756

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000362

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000754

AC:

1102

AN:

1460934

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

438

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.0284

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00693

AC:

1056

AN:

152328

Hom.:

Cov.:

AF XY:

0.00683

AC XY:

509

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0246

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00300

Hom.:

Bravo

AF:

0.00777

ESP6500AA

AF:

0.0265

AC:

116

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00224

AC:

272

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.28

T;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.20

Sift

Benign

0.30

T;T

Sift4G

Benign

0.085

T;T

Polyphen

0.90

P;P

Vest4

0.14

MVP

0.82

MPC

0.090

ClinPred

0.0024

GERP RS

-1.3

Varity_R

0.033

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over