Variant 8-23224856-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000221132.8(TNFRSF10A):c.206G>C(p.Arg69Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,568,778 control chromosomes in the GnomAD database, including 21 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 0.0025 ( 3 hom., cov: 30)

Exomes 𝑓: 0.0029 ( 18 hom. )

Consequence

TNFRSF10A
ENST00000221132.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.916

Variant links:

Genes affected

TNFRSF10A (HGNC:11904): (TNF receptor superfamily member 10a) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [provided by RefSeq, Jul 2008]

TNFRSF10A links:

TNFRSF10A-DT (HGNC:52647): (TNFRSF10A divergent transcript)

TNFRSF10A-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041168034).

BP6

Variant 8-23224856-C-G is Benign according to our data. Variant chr8-23224856-C-G is described in ClinVar as [Benign]. Clinvar id is 730510.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 386 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4 linkuse as main transcript	c.206G>C	p.Arg69Pro	missense_variant	1/10	ENST00000221132.8	NP_003835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TNFRSF10A	ENST00000221132.8 linkuse as main transcript	c.206G>C	p.Arg69Pro	missense_variant	1/10	1	NM_003844.4	ENSP00000221132	P1
TNFRSF10A	ENST00000613472.1 linkuse as main transcript	c.31+175G>C		intron_variant		1		ENSP00000480778
TNFRSF10A-DT	ENST00000517774.1 linkuse as main transcript	n.386C>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.00253

AC:

385

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00253

AC:

436

AN:

172054

Hom.:

AF XY:

0.00248

AC XY:

231

AN XY:

93200

show subpopulations

Gnomad AFR exome

AF:

0.000219

Gnomad AMR exome

AF:

0.000822

Gnomad ASJ exome

AF:

0.00117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.00255

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00289

AC:

4094

AN:

1416696

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

2033

AN XY:

700474

show subpopulations

Gnomad4 AFR exome

AF:

0.000308

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00146

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.00289

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00254

AC:

386

AN:

152082

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00300

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00195

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00121

AC:

ExAC

AF:

0.00167

AC:

197

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.0

DANN

Benign

0.65

DEOGEN2

Benign

0.0020

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.080

REVEL

Benign

0.16

Sift

Benign

0.20

Sift4G

Benign

0.29

Polyphen

0.0050

Vest4

0.12

MVP

0.19

MPC

0.12

ClinPred

0.00056

GERP RS

-3.1

Varity_R

0.10

gMVP

0.22

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