rs77874543

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_052945.4(TNFRSF13C):c.62C>G(p.Pro21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 1,449,142 control chromosomes in the GnomAD database, including 4,214 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.056 ( 301 hom., cov: 32)

Exomes 𝑓: 0.076 ( 3913 hom. )

Consequence

TNFRSF13C
NM_052945.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: -0.668

Publications

34 publications found

Variant links:

Genes affected

TNFRSF13C (HGNC:17755): (TNF receptor superfamily member 13C) B cell-activating factor (BAFF) enhances B-cell survival in vitro and is a regulator of the peripheral B-cell population. Overexpression of Baff in mice results in mature B-cell hyperplasia and symptoms of systemic lupus erythematosus (SLE). Also, some SLE patients have increased levels of BAFF in serum. Therefore, it has been proposed that abnormally high levels of BAFF may contribute to the pathogenesis of autoimmune diseases by enhancing the survival of autoreactive B cells. The protein encoded by this gene is a receptor for BAFF and is a type III transmembrane protein containing a single extracellular cysteine-rich domain. It is thought that this receptor is the principal receptor required for BAFF-mediated mature B-cell survival. [provided by RefSeq, Jul 2008]

TNFRSF13C Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 4
Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
common variable immunodeficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TNFRSF13C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002217114).

BP6

Variant 22-41926712-G-C is Benign according to our data. Variant chr22-41926712-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 341883.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052945.4. 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
	TNFRSF13C	NM_052945.4	MANE Select	c.62C>G	p.Pro21Arg	missense	Exon 1 of 3	NP_443177.1	Q5H8V1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13C	ENST00000291232.5	TSL:1 MANE Select	c.62C>G	p.Pro21Arg	missense	Exon 1 of 3	ENSP00000291232.3	Q96RJ3-1
	TNFRSF13C	ENST00000898406.1		c.62C>G	p.Pro21Arg	missense	Exon 1 of 3	ENSP00000568465.1

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8506

AN:

152018

Hom.:

302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.0574

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.0427

Gnomad SAS

AF:

0.0608

Gnomad FIN

AF:

0.0777

Gnomad MID

AF:

0.0385

Gnomad NFE

AF:

0.0794

Gnomad OTH

AF:

0.0598

GnomAD2 exomes

AF:

0.0607

AC:

4113

AN:

67812

AF XY:

0.0628

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.0364

Gnomad ASJ exome

AF:

0.0477

Gnomad EAS exome

AF:

0.0346

Gnomad FIN exome

AF:

0.0806

Gnomad NFE exome

AF:

0.0772

Gnomad OTH exome

AF:

0.0566

GnomAD4 exome

AF:

0.0757

AC:

98190

AN:

1297018

Hom.:

3913

Cov.:

AF XY:

0.0751

AC XY:

47951

AN XY:

638164

show subpopulations

African (AFR)

AF:

0.0105

AC:

276

AN:

26168

American (AMR)

AF:

0.0430

AC:

1029

AN:

23948

Ashkenazi Jewish (ASJ)

AF:

0.0485

AC:

1095

AN:

22562

East Asian (EAS)

AF:

0.0477

AC:

1329

AN:

27888

South Asian (SAS)

AF:

0.0610

AC:

4228

AN:

69330

European-Finnish (FIN)

AF:

0.0840

AC:

2723

AN:

32400

Middle Eastern (MID)

AF:

0.0523

AC:

201

AN:

3844

European-Non Finnish (NFE)

AF:

0.0807

AC:

83739

AN:

1037274

Other (OTH)

AF:

0.0666

AC:

3570

AN:

53604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

5027

10055

15082

20110

25137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3200

6400

9600

12800

16000

<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:

0.0559

AC:

8501

AN:

152124

Hom.:

301

Cov.:

AF XY:

0.0556

AC XY:

4133

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0136

AC:

566

AN:

41548

American (AMR)

AF:

0.0572

AC:

875

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

155

AN:

3472

East Asian (EAS)

AF:

0.0429

AC:

220

AN:

5132

South Asian (SAS)

AF:

0.0606

AC:

293

AN:

4832

European-Finnish (FIN)

AF:

0.0777

AC:

822

AN:

10578

Middle Eastern (MID)

AF:

0.0345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0794

AC:

5398

AN:

67956

Other (OTH)

AF:

0.0587

AC:

124

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

426

853

1279

1706

2132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0690

Hom.:

Bravo

AF:

0.0513

TwinsUK

AF:

0.0850

AC:

315

ALSPAC

AF:

0.0760

AC:

293

ESP6500AA

AF:

0.00439

AC:

ESP6500EA

AF:

0.0319

AC:

118

ExAC

AF:

0.0270

AC:

705

Asia WGS

AF:

0.0610

AC:

209

AN:

3466

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency, common variable, 4 (3)

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.26

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

-0.67

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.7

REVEL

Benign

0.026

Sift

Benign

0.27

Sift4G

Benign

0.33

Polyphen

0.18

Vest4

0.032

MPC

1.3

ClinPred

0.00063

GERP RS

0.12

PromoterAI

0.022

Neutral

(source)

Varity_R

0.13

gMVP

0.047

Mutation Taster

=97/3

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

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