chr8-23200707-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003844.4(TNFRSF10A):c.683A>C(p.Glu228Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,605,418 control chromosomes in the GnomAD database, including 28,771 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1965 hom., cov: 31)

Exomes 𝑓: 0.19 ( 26806 hom. )

Consequence

TNFRSF10A
NM_003844.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.03

Publications

65 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010643601).

BP6

Variant 8-23200707-T-G is Benign according to our data. Variant chr8-23200707-T-G is described in ClinVar as Benign. ClinVar VariationId is 1253334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10A	NM_003844.4 link	c.683A>C	p.Glu228Ala	missense_variant	Exon 5 of 10	ENST00000221132.8	NP_003835.3	O00220

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNFRSF10A	ENST00000221132.8 link	c.683A>C	p.Glu228Ala	missense_variant	Exon 5 of 10	1	NM_003844.4	ENSP00000221132.3	O00220
TNFRSF10A	ENST00000613472.1 link	c.209A>C	p.Glu70Ala	missense_variant	Exon 4 of 9	1		ENSP00000480778.1	F8U8C0
TNFRSF10A	ENST00000524158.5 link	c.77A>C	p.Glu26Ala	missense_variant	Exon 5 of 7	5		ENSP00000428884.1	E5RFH1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21716

AN:

151290

Hom.:

1965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0927

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.162

GnomAD2 exomes

AF:

0.151

AC:

38009

AN:

251454

AF XY:

0.155

show subpopulations

Gnomad AFR exome

AF:

0.0317

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.185

AC:

269208

AN:

1454004

Hom.:

26806

Cov.:

AF XY:

0.183

AC XY:

132429

AN XY:

723542

show subpopulations

African (AFR)

AF:

0.0320

AC:

1055

AN:

32938

American (AMR)

AF:

0.111

AC:

4949

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5156

AN:

25846

East Asian (EAS)

AF:

0.0148

AC:

578

AN:

38964

South Asian (SAS)

AF:

0.0925

AC:

7973

AN:

86186

European-Finnish (FIN)

AF:

0.216

AC:

11365

AN:

52542

Middle Eastern (MID)

AF:

0.181

AC:

1037

AN:

5736

European-Non Finnish (NFE)

AF:

0.205

AC:

226902

AN:

1107580

Other (OTH)

AF:

0.171

AC:

10193

AN:

59758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

12040

24080

36120

48160

60200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7664

15328

22992

30656

38320

<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:

0.143

AC:

21712

AN:

151414

Hom.:

1965

Cov.:

AF XY:

0.144

AC XY:

10647

AN XY:

73964

show subpopulations

African (AFR)

AF:

0.0377

AC:

1559

AN:

41316

American (AMR)

AF:

0.143

AC:

2174

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

707

AN:

3466

East Asian (EAS)

AF:

0.0161

AC:

AN:

5108

South Asian (SAS)

AF:

0.0933

AC:

445

AN:

4768

European-Finnish (FIN)

AF:

0.231

AC:

2408

AN:

10434

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13710

AN:

67798

Other (OTH)

AF:

0.160

AC:

336

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

916

1831

2747

3662

4578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.177

Hom.:

8638

Bravo

AF:

0.134

TwinsUK

AF:

0.206

AC:

764

ALSPAC

AF:

0.195

AC:

753

ESP6500AA

AF:

0.0470

AC:

207

ESP6500EA

AF:

0.200

AC:

1720

ExAC

AF:

0.149

AC:

18104

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

EpiCase

AF:

0.210

EpiControl

AF:

0.217

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 21484799, 23658636, 22401174) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.57

D;D;D

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.51

T;T;T

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.

PhyloP100

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.3

N;.;D

REVEL

Benign

0.11

Sift

Benign

0.037

D;.;D

Sift4G

Uncertain

0.053

T;D;T

Polyphen

0.31

B;.;.

Vest4

0.13

MPC

0.12

ClinPred

0.0099

GERP RS

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.61

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over