Genetic Variant TNFSF10:c.*662T>C (chr3-172505830-A-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.*662T>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 0.695 in 151,064 control chromosomes in the GnomAD database, including 36,860 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 ( 36860 hom., cov: 27)

Exomes 𝑓: 0.75 ( 18 hom. )

Failed GnomAD Quality Control

Consequence

TNFSF10
NM_003810.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792

Publications

36 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=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNFSF10	NM_003810.4 link	c.*662T>C	3_prime_UTR_variant	Exon 5 of 5	ENST00000241261.7	NP_003801.1	P50591-1Q6IBA9
TNFSF10	NR_033994.2 link	n.1511T>C	non_coding_transcript_exon_variant	Exon 4 of 4
TNFSF10	NM_001190942.2 link	c.*1054T>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.*662T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_003810.4	ENSP00000241261.2		P50591-1
TNFSF10	ENST00000420541.6 link	c.*1054T>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000389931.2		P50591-2

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

104918

AN:

150946

Hom.:

36845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.799

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.706

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.694

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.760

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.695

AC:

104981

AN:

151064

Hom.:

36860

Cov.:

AF XY:

0.692

AC XY:

51025

AN XY:

73744

show subpopulations

African (AFR)

AF:

0.778

AC:

32008

AN:

41138

American (AMR)

AF:

0.569

AC:

8633

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

2514

AN:

3458

East Asian (EAS)

AF:

0.633

AC:

3227

AN:

5096

South Asian (SAS)

AF:

0.636

AC:

3048

AN:

4790

European-Finnish (FIN)

AF:

0.702

AC:

7256

AN:

10340

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.677

AC:

45885

AN:

67784

Other (OTH)

AF:

0.703

AC:

1467

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1572

3144

4716

6288

7860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.684

Hom.:

4213

Bravo

AF:

0.687

Asia WGS

AF:

0.652

AC:

2265

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.9

(source)

DANN

Benign

0.40

PhyloP100

-0.79

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over