Variant 3-172523209-T-G 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_003810.4(TNFSF10):c.132+44A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,533,212 control chromosomes in the GnomAD database, including 31,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2993 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28157 hom. )

Consequence

TNFSF10
NM_003810.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0480

Variant links:

Genes affected

TNFSF10 (HGNC:11925): (TNF superfamily member 10) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

TNFSF10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-172523209-T-G is Benign according to our data. Variant chr3-172523209-T-G is described in ClinVar as [Benign]. Clinvar id is 1288782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
TNFSF10	NM_003810.4 linkuse as main transcript	c.132+44A>C	intron_variant	ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2 linkuse as main transcript	c.132+44A>C	intron_variant		NP_001177871.1
TNFSF10	NM_001190943.2 linkuse as main transcript	c.132+44A>C	intron_variant		NP_001177872.1
TNFSF10	NR_033994.2 linkuse as main transcript	n.178+44A>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7 linkuse as main transcript	c.132+44A>C		intron_variant		1	NM_003810.4	ENSP00000241261	P1	P50591-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27174

AN:

152040

Hom.:

2994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.218

AC:

51462

AN:

235886

Hom.:

7154

AF XY:

0.222

AC XY:

28313

AN XY:

127814

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.546

Gnomad SAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.188

AC:

259782

AN:

1381054

Hom.:

28157

Cov.:

AF XY:

0.191

AC XY:

130081

AN XY:

680070

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.314

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.195

GnomAD4 genome

AF:

0.179

AC:

27192

AN:

152158

Hom.:

2993

Cov.:

AF XY:

0.185

AC XY:

13759

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.544

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.171

Hom.:

5261

Bravo

AF:

0.170

Asia WGS

AF:

0.441

AC:

1527

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 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.8

DANN

Benign

0.27

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