rs11552708

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003808.4(TNFSF13):c.199G>A(p.Gly67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,609,662 control chromosomes in the GnomAD database, including 14,667 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1232 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13435 hom. )

Consequence

TNFSF13
NM_003808.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

TNFSF13 (HGNC:11928): (TNF superfamily member 13) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM. Alternative splicing results in multiple transcript variants. Some transcripts that skip the last exon of the upstream gene (TNFSF12) and continue into the second exon of this gene have been identified; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

TNFSF13 links:

TNFSF12-TNFSF13 (HGNC:):

TNFSF12-TNFSF13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029675663).

BP6

Variant 17-7559238-G-A is Benign according to our data. Variant chr17-7559238-G-A is described in ClinVar as [Benign]. Clinvar id is 1181749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13	NM_003808.4 linkuse as main transcript	c.199G>A	p.Gly67Arg	missense_variant	1/6	ENST00000338784.9	NP_003799.1
TNFSF12-TNFSF13	NM_172089.4 linkuse as main transcript	c.499-386G>A		intron_variant			NP_742086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13	ENST00000338784.9 linkuse as main transcript	c.199G>A	p.Gly67Arg	missense_variant	1/6	1	NM_003808.4	ENSP00000343505	P3	O75888-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17521

AN:

152118

Hom.:

1227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.0718

Gnomad FIN

AF:

0.0707

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.132

AC:

31752

AN:

240328

Hom.:

2706

AF XY:

0.125

AC XY:

16465

AN XY:

131372

show subpopulations

Gnomad AFR exome

AF:

0.0849

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.329

Gnomad SAS exome

AF:

0.0619

Gnomad FIN exome

AF:

0.0752

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.126

AC:

183442

AN:

1457426

Hom.:

13435

Cov.:

AF XY:

0.123

AC XY:

88819

AN XY:

724914

show subpopulations

Gnomad4 AFR exome

AF:

0.0844

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.370

Gnomad4 SAS exome

AF:

0.0620

Gnomad4 FIN exome

AF:

0.0778

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.115

AC:

17537

AN:

152236

Hom.:

1232

Cov.:

AF XY:

0.114

AC XY:

8520

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0874

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.325

Gnomad4 SAS

AF:

0.0723

Gnomad4 FIN

AF:

0.0707

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.109

Hom.:

1591

Bravo

AF:

0.129

TwinsUK

AF:

0.121

AC:

448

ALSPAC

AF:

0.130

AC:

500

ESP6500AA

AF:

0.0828

AC:

356

ESP6500EA

AF:

0.110

AC:

932

ExAC

AF:

0.127

AC:

15299

Asia WGS

AF:

0.160

AC:

555

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 23118916) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.019

.;.;T;.;.;T;.;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.094

T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.7

.;.;.;.;N;N;N;N

MutationTaster

Benign

8.6e-9

P;P;P;P;P;P;P;P

PROVEAN

Benign

-0.090

N;N;N;N;N;N;.;N

REVEL

Uncertain

0.34

Sift

Benign

0.42

T;T;T;T;T;T;.;T

Sift4G

Benign

0.82

T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;B;B;.;B

Vest4

0.070

MutPred

0.088

Gain of solvent accessibility (P = 0.0037);.;.;.;Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);

MPC

0.38

ClinPred

0.0037

GERP RS

2.2

Varity_R

0.042

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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