Genetic Variant TNFRSF21:p.Pro542Pro (chr6-47234782-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014452.5(TNFRSF21):c.1626A>G(p.Pro542Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,598,998 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 3 hom. )

Consequence

TNFRSF21
NM_014452.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.52

Publications

0 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-47234782-T-C is Benign according to our data. Variant chr6-47234782-T-C is described in ClinVar as Benign. ClinVar VariationId is 721586.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.52 with no splicing effect.

BS2

High AC in GnomAd4 at 390 AD gene.

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.1626A>G	p.Pro542Pro	synonymous	Exon 5 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.1626A>G	p.Pro542Pro	synonymous	Exon 5 of 6	ENSP00000296861.2	O75509
TNFRSF21	ENST00000877798.1		c.1704A>G	p.Pro568Pro	synonymous	Exon 6 of 7	ENSP00000547857.1
TNFRSF21	ENST00000952535.1		c.1131A>G	p.Pro377Pro	synonymous	Exon 4 of 5	ENSP00000622594.1

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

389

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00899

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000609

AC:

141

AN:

231624

AF XY:

0.000470

show subpopulations

Gnomad AFR exome

AF:

0.00833

Gnomad AMR exome

AF:

0.000502

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.000232

AC:

336

AN:

1446834

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

157

AN XY:

719266

show subpopulations

African (AFR)

AF:

0.00837

AC:

272

AN:

32514

American (AMR)

AF:

0.000483

AC:

AN:

41434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25702

East Asian (EAS)

AF:

0.00

AC:

AN:

38732

South Asian (SAS)

AF:

0.0000240

AC:

AN:

83236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1106666

Other (OTH)

AF:

0.000468

AC:

AN:

59808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00256

AC:

390

AN:

152164

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00898

AC:

373

AN:

41514

American (AMR)

AF:

0.000981

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00114

Hom.:

Bravo

AF:

0.00278

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

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.041

(source)

DANN

Benign

0.31

PhyloP100

-4.5

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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