Variant 8-23200675-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003844.4(TNFRSF10A):c.703+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,609,744 control chromosomes in the GnomAD database, including 71,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7284 hom., cov: 31)

Exomes 𝑓: 0.29 ( 64582 hom. )

Consequence

TNFRSF10A
NM_003844.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0290

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 8-23200675-T-C is Benign according to our data. Variant chr8-23200675-T-C is described in ClinVar as [Benign]. Clinvar id is 1241396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10A	NM_003844.4 linkuse as main transcript	c.703+12A>G		intron_variant		ENST00000221132.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
TNFRSF10A	ENST00000221132.8 linkuse as main transcript	c.703+12A>G	intron_variant	1	NM_003844.4	P1
TNFRSF10A	ENST00000613472.1 linkuse as main transcript	c.229+12A>G	intron_variant	1
TNFRSF10A	ENST00000524158.5 linkuse as main transcript	c.97+12A>G	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

45988

AN:

151416

Hom.:

7281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.0580

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.284

GnomAD3 exomes

AF:

0.291

AC:

73073

AN:

251406

Hom.:

11558

AF XY:

0.286

AC XY:

38896

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.0516

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.294

AC:

428147

AN:

1458208

Hom.:

64582

Cov.:

AF XY:

0.292

AC XY:

211924

AN XY:

725456

show subpopulations

Gnomad4 AFR exome

AF:

0.326

Gnomad4 AMR exome

AF:

0.383

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.0749

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.351

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.304

AC:

45996

AN:

151536

Hom.:

7284

Cov.:

AF XY:

0.302

AC XY:

22350

AN XY:

74030

show subpopulations

Gnomad4 AFR

AF:

0.320

Gnomad4 AMR

AF:

0.346

Gnomad4 ASJ

AF:

0.242

Gnomad4 EAS

AF:

0.0583

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.294

Hom.:

13760

Bravo

AF:

0.302

Asia WGS

AF:

0.152

AC:

534

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 18, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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