6-47284022-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014452.5(TNFRSF21):c.1159G>A(p.Ala387Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,614,180 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 163 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 131 hom. )

Consequence

TNFRSF21
NM_014452.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.187

Publications

6 publications found

Variant links:

Genes affected

TNFRSF21 (HGNC:13469): (TNF receptor superfamily member 21) This gene encodes a member of the tumor necrosis factor receptor superfamily. The encoded protein activates nuclear factor kappa-B and mitogen-activated protein kinase 8 (also called c-Jun N-terminal kinase 1), and induces cell apoptosis. Through its death domain, the encoded receptor interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD) protein, which is known to mediate signal transduction of tumor necrosis factor receptors. Knockout studies in mice suggest that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. [provided by RefSeq, Jul 2013]

TNFRSF21 Gene-Disease associations (from GenCC):

myopia
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

TNFRSF21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016060174).

BP6

Variant 6-47284022-C-T is Benign according to our data. Variant chr6-47284022-C-T is described in ClinVar as Benign. ClinVar VariationId is 788536.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014452.5. 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
	TNFRSF21	NM_014452.5	MANE Select	c.1159G>A	p.Ala387Thr	missense	Exon 3 of 6	NP_055267.1	O75509

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFRSF21	ENST00000296861.2	TSL:1 MANE Select	c.1159G>A	p.Ala387Thr	missense	Exon 3 of 6	ENSP00000296861.2	O75509
TNFRSF21	ENST00000877798.1		c.1159G>A	p.Ala387Thr	missense	Exon 3 of 7	ENSP00000547857.1
TNFRSF21	ENST00000952536.1		c.1159G>A	p.Ala387Thr	missense	Exon 3 of 6	ENSP00000622595.1

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3632

AN:

152182

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0839

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00656

AC:

1650

AN:

251426

AF XY:

0.00498

show subpopulations

Gnomad AFR exome

AF:

0.0866

Gnomad AMR exome

AF:

0.00500

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00249

AC:

3647

AN:

1461880

Hom.:

131

Cov.:

AF XY:

0.00216

AC XY:

1568

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0867

AC:

2902

AN:

33476

American (AMR)

AF:

0.00528

AC:

236

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00102

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000863

AC:

AN:

1112012

Other (OTH)

AF:

0.00515

AC:

311

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

219

438

656

875

1094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.0239

AC:

3636

AN:

152300

Hom.:

163

Cov.:

AF XY:

0.0229

AC XY:

1707

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0838

AC:

3481

AN:

41562

American (AMR)

AF:

0.00660

AC:

101

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68030

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

175

350

525

700

875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00820

Hom.:

103

Bravo

AF:

0.0273

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0792

AC:

349

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00781

AC:

948

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.6

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-0.19

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.58

REVEL

Benign

0.14

Sift

Benign

0.19

Sift4G

Uncertain

0.016

Polyphen

0.0010

Vest4

0.11

MVP

0.11

MPC

0.27

ClinPred

0.0050

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.37

Mutation Taster

=85/15

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over