rs74811083

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_012452.3(TNFRSF13B):c.563A>T(p.Lys188Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,611,408 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K188T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.015 ( 52 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 60 hom. )

Consequence

TNFRSF13B
NM_012452.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.140

Publications

8 publications found

Variant links:

Genes affected

TNFRSF13B (HGNC:18153): (TNF receptor superfamily member 13B) The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

TNFRSF13B Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, G2P, Ambry Genetics
common variable immunodeficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TNFRSF13B links:

ENSG00000307457 (HGNC:):

ENSG00000307457 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=0.0057032406).

BP6

Variant 17-16940394-T-A is Benign according to our data. Variant chr17-16940394-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012452.3. 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
	TNFRSF13B	NM_012452.3	MANE Select	c.563A>T	p.Lys188Met	missense	Exon 4 of 5	NP_036584.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNFRSF13B	ENST00000261652.7	TSL:1 MANE Select	c.563A>T	p.Lys188Met	missense	Exon 4 of 5	ENSP00000261652.2
TNFRSF13B	ENST00000583789.1	TSL:1	c.425A>T	p.Lys142Met	missense	Exon 3 of 4	ENSP00000462952.1
TNFRSF13B	ENST00000579315.5	TSL:3	c.446-7218A>T		intron	N/A	ENSP00000464069.1

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2206

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000646

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0101

GnomAD2 exomes

AF:

0.00346

AC:

868

AN:

250762

AF XY:

0.00249

show subpopulations

Gnomad AFR exome

AF:

0.0496

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00144

AC:

2107

AN:

1459396

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

891

AN XY:

725466

show subpopulations

African (AFR)

AF:

0.0542

AC:

1813

AN:

33476

American (AMR)

AF:

0.00177

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000714

AC:

AN:

84006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00158

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

1112000

Other (OTH)

AF:

0.00260

AC:

157

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

138

277

415

554

692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0145

AC:

2207

AN:

152012

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1017

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.0507

AC:

2103

AN:

41518

American (AMR)

AF:

0.00431

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000646

AC:

AN:

4644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

67994

Other (OTH)

AF:

0.00997

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

103

205

308

410

513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00111

Hom.:

Bravo

AF:

0.0158

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0493

AC:

217

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00463

AC:

560

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Common Variable Immune Deficiency, Dominant (1)

Immunodeficiency, common variable, 2 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Uncertain

0.67

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0057

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

0.69

PhyloP100

0.14

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.40

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.88

Vest4

0.42

MVP

0.78

MPC

0.054

ClinPred

0.061

GERP RS

2.4

Varity_R

0.17

gMVP

0.31

Mutation Taster

=98/2

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