Genetic Variant TNFSF10:c.*356A>C (chr3-172506136-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003810.4(TNFSF10):c.*356A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 186,856 control chromosomes in the GnomAD database, including 44,728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 37042 hom., cov: 32)

Exomes 𝑓: 0.65 ( 7686 hom. )

Consequence

TNFSF10
NM_003810.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.295

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNFSF10	NM_003810.4 link	c.*356A>C	3_prime_UTR_variant	Exon 5 of 5	ENST00000241261.7	NP_003801.1	P50591-1Q6IBA9
TNFSF10	NR_033994.2 link	n.1205A>C	non_coding_transcript_exon_variant	Exon 4 of 4
TNFSF10	NM_001190942.2 link	c.*748A>C	3_prime_UTR_variant	Exon 3 of 3		NP_001177871.1	P50591-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7 link	c.*356A>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_003810.4	ENSP00000241261.2		P50591-1
TNFSF10	ENST00000420541.6 link	c.*748A>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000389931.2		P50591-2

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105500

AN:

151902

Hom.:

37027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.787

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.704

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.707

GnomAD4 exome

AF:

0.654

AC:

22783

AN:

34836

Hom.:

7686

Cov.:

AF XY:

0.652

AC XY:

11804

AN XY:

18092

show subpopulations

African (AFR)

AF:

0.771

AC:

597

AN:

774

American (AMR)

AF:

0.513

AC:

1159

AN:

2258

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

690

AN:

952

East Asian (EAS)

AF:

0.588

AC:

992

AN:

1686

South Asian (SAS)

AF:

0.640

AC:

1664

AN:

2600

European-Finnish (FIN)

AF:

0.694

AC:

877

AN:

1264

Middle Eastern (MID)

AF:

0.764

AC:

AN:

110

European-Non Finnish (NFE)

AF:

0.663

AC:

15348

AN:

23142

Other (OTH)

AF:

0.669

AC:

1372

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

377

755

1132

1510

1887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.694

AC:

105563

AN:

152020

Hom.:

37042

Cov.:

AF XY:

0.692

AC XY:

51399

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.775

AC:

32132

AN:

41442

American (AMR)

AF:

0.568

AC:

8665

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

2518

AN:

3468

East Asian (EAS)

AF:

0.633

AC:

3281

AN:

5182

South Asian (SAS)

AF:

0.636

AC:

3063

AN:

4818

European-Finnish (FIN)

AF:

0.704

AC:

7433

AN:

10564

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.677

AC:

46036

AN:

67966

Other (OTH)

AF:

0.704

AC:

1486

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1631

3262

4892

6523

8154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.671

Hom.:

12853

Bravo

AF:

0.686

Asia WGS

AF:

0.649

AC:

2256

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.3

(source)

DANN

Benign

0.81

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over