dbSNP rs35975099: TNFSF10:c.*1075_*1076insTCAC (chr3-172505416-G-GGTGA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003810.4(TNFSF10):c.*1075_*1076insTCAC variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,354 control chromosomes in the GnomAD database, including 36,987 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 36987 hom., cov: 0)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

TNFSF10
NM_003810.4 downstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.794

Publications

5 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TNFSF10	NM_003810.4	MANE Select	c.1075_1076insTCAC	downstream_gene	N/A	NP_003801.1
TNFSF10	NM_001190942.2		c.1467_1468insTCAC	downstream_gene	N/A	NP_001177871.1
TNFSF10	NR_033994.2		n.91_92insTCAC	downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.1075_1076insTCAC		downstream_gene	N/A	ENSP00000241261.2
	TNFSF10	ENST00000420541.6	TSL:1	c.1467_1468insTCAC		downstream_gene	N/A	ENSP00000389931.2

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105176

AN:

151230

Hom.:

36972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

0.786

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.799

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.708

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.695

AC:

105240

AN:

151350

Hom.:

36987

Cov.:

AF XY:

0.692

AC XY:

51188

AN XY:

73934

show subpopulations

African (AFR)

AF:

0.779

AC:

32105

AN:

41204

American (AMR)

AF:

0.569

AC:

8651

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

2522

AN:

3468

East Asian (EAS)

AF:

0.631

AC:

3245

AN:

5140

South Asian (SAS)

AF:

0.636

AC:

3046

AN:

4788

European-Finnish (FIN)

AF:

0.701

AC:

7308

AN:

10420

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.677

AC:

45944

AN:

67834

Other (OTH)

AF:

0.705

AC:

1476

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1523

3047

4570

6094

7617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.693

Hom.:

3938

Asia WGS

AF:

0.650

AC:

2254

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.79

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over