Genetic Variant TNFRSF10A:c.403+2089A>G (chr8-23210027-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003844.4(TNFRSF10A):c.403+2089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,172 control chromosomes in the GnomAD database, including 3,543 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 0.20 ( 3543 hom., cov: 32)

Consequence

TNFRSF10A
NM_003844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.147

Publications

2 publications found

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:

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new If you want to explore the variant's impact on the transcript NM_003844.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10A	NM_003844.4	MANE Select	c.403+2089A>G		intron	N/A	NP_003835.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNFRSF10A	ENST00000221132.8	TSL:1 MANE Select	c.403+2089A>G	intron	N/A	ENSP00000221132.3	O00220
TNFRSF10A	ENST00000613472.1	TSL:1	c.32-7368A>G	intron	N/A	ENSP00000480778.1	F8U8C0
TNFRSF10A	ENST00000901503.1		c.403+2089A>G	intron	N/A	ENSP00000571562.1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29761

AN:

152054

Hom.:

3540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0598

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.196

AC:

29774

AN:

152172

Hom.:

3543

Cov.:

AF XY:

0.200

AC XY:

14897

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0598

AC:

2486

AN:

41548

American (AMR)

AF:

0.308

AC:

4705

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

930

AN:

3470

East Asian (EAS)

AF:

0.300

AC:

1548

AN:

5162

South Asian (SAS)

AF:

0.364

AC:

1755

AN:

4824

European-Finnish (FIN)

AF:

0.204

AC:

2156

AN:

10590

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15433

AN:

67984

Other (OTH)

AF:

0.216

AC:

456

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1201

2401

3602

4802

6003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.199

Hom.:

446

Bravo

AF:

0.195

Asia WGS

AF:

0.316

AC:

1097

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.0

(source)

DANN

Benign

0.82

PhyloP100

0.15

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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