Variant 8-23191695-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_003844.4(TNFRSF10A):c.1406G>T(p.Ter469Leuext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000875 in 1,610,852 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 3 hom. )

Consequence

TNFRSF10A
NM_003844.4 stop_lost

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.240

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Stoplost variant in NM_003844.4 Downstream stopcodon found after 1 codons.

BP6

Variant 8-23191695-C-A is Benign according to our data. Variant chr8-23191695-C-A is described in ClinVar as [Benign]. Clinvar id is 784502.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4 linkuse as main transcript	c.1406G>T	p.Ter469Leuext*?	stop_lost	10/10	ENST00000221132.8	NP_003835.3	O00220

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10A	ENST00000221132.8 linkuse as main transcript	c.1406G>T	p.Ter469Leuext*?	stop_lost	10/10	1	NM_003844.4	ENSP00000221132.3		O00220
TNFRSF10A	ENST00000613472.1 linkuse as main transcript	c.932G>T	p.Ter311Leuext*?	stop_lost	9/9	1		ENSP00000480778.1		F8U8C0

Frequencies

GnomAD3 genomes

AF:

0.000796

AC:

121

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00131

AC:

325

AN:

247736

Hom.:

AF XY:

0.00131

AC XY:

176

AN XY:

134030

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.0000937

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00216

GnomAD4 exome

AF:

0.000883

AC:

1288

AN:

1458698

Hom.:

Cov.:

AF XY:

0.000912

AC XY:

662

AN XY:

725526

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.0000564

Gnomad4 NFE exome

AF:

0.000652

Gnomad4 OTH exome

AF:

0.00184

GnomAD4 genome

AF:

0.000795

AC:

121

AN:

152154

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.000960

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00119

AC:

145

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00154

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

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.41

DANN

Benign

0.72

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.018

Vest4

0.16

GERP RS

-1.7

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