Variant 6-47234828-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_014452.5(TNFRSF21):c.1580A>G(p.Asn527Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,545,374 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

TNFRSF21
NM_014452.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.923

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004008323).

BP6

Variant 6-47234828-T-C is Benign according to our data. Variant chr6-47234828-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3352684.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF21	NM_014452.5 linkuse as main transcript	c.1580A>G	p.Asn527Ser	missense_variant	5/6	ENST00000296861.2	NP_055267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF21	ENST00000296861.2 linkuse as main transcript	c.1580A>G	p.Asn527Ser	missense_variant	5/6	1	NM_014452.5	ENSP00000296861	P1

Frequencies

GnomAD3 genomes

AF:

0.000908

AC:

138

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000887

AC:

151

AN:

170260

Hom.:

AF XY:

0.000921

AC XY:

AN XY:

92286

show subpopulations

Gnomad AFR exome

AF:

0.000290

Gnomad AMR exome

AF:

0.000591

Gnomad ASJ exome

AF:

0.00162

Gnomad EAS exome

AF:

0.0000904

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000340

Gnomad NFE exome

AF:

0.00145

Gnomad OTH exome

AF:

0.000732

GnomAD4 exome

AF:

0.00114

AC:

1589

AN:

1393254

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

769

AN XY:

688452

show subpopulations

Gnomad4 AFR exome

AF:

0.0000333

Gnomad4 AMR exome

AF:

0.000960

Gnomad4 ASJ exome

AF:

0.00118

Gnomad4 EAS exome

AF:

0.0000855

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.000465

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.000956

GnomAD4 genome

AF:

0.000907

AC:

138

AN:

152120

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000969

Hom.:

Bravo

AF:

0.00106

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000752

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TNFRSF21-related condition

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 28, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.33

DEOGEN2

Benign

0.14

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.74

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.38

REVEL

Benign

0.12

Sift

Benign

0.30

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.20

MVP

0.093

MPC

0.22

ClinPred

0.0058

GERP RS

1.1

Varity_R

0.036

gMVP

0.096

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over