rs7290134

Variant names:

Variant summary

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

The NM_052945.4(TNFRSF13C):c.*120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,103,354 control chromosomes in the GnomAD database, including 55,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 18242 hom., cov: 32)

Exomes 𝑓: 0.25 ( 37108 hom. )

Consequence

TNFRSF13C
NM_052945.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.681

Publications

21 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):

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

TNFRSF13C 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 (BayesDel_noAF=-0.89).

BP6

Variant 22-41925247-A-G is Benign according to our data. Variant chr22-41925247-A-G is described in ClinVar as Benign. ClinVar VariationId is 341874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13C	NM_052945.4 link	c.*120T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000291232.5	NP_443177.1	Q96RJ3-1Q5H8V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13C	ENST00000291232.5 link	c.*120T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_052945.4	ENSP00000291232.3		Q96RJ3-1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

62078

AN:

152016

Hom.:

18175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.817

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.375

GnomAD4 exome

AF:

0.253

AC:

241121

AN:

951220

Hom.:

37108

Cov.:

AF XY:

0.254

AC XY:

120678

AN XY:

475028

show subpopulations

African (AFR)

AF:

0.840

AC:

18565

AN:

22112

American (AMR)

AF:

0.547

AC:

12873

AN:

23542

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

4977

AN:

17602

East Asian (EAS)

AF:

0.105

AC:

3508

AN:

33388

South Asian (SAS)

AF:

0.348

AC:

20541

AN:

58970

European-Finnish (FIN)

AF:

0.204

AC:

6192

AN:

30378

Middle Eastern (MID)

AF:

0.302

AC:

901

AN:

2986

European-Non Finnish (NFE)

AF:

0.224

AC:

161155

AN:

719580

Other (OTH)

AF:

0.291

AC:

12409

AN:

42662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

8590

17180

25769

34359

42949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5276

10552

15828

21104

26380

<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:

0.409

AC:

62198

AN:

152134

Hom.:

18242

Cov.:

AF XY:

0.405

AC XY:

30145

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.818

AC:

33917

AN:

41488

American (AMR)

AF:

0.462

AC:

7053

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

974

AN:

3470

East Asian (EAS)

AF:

0.117

AC:

608

AN:

5176

South Asian (SAS)

AF:

0.358

AC:

1727

AN:

4824

European-Finnish (FIN)

AF:

0.195

AC:

2064

AN:

10590

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14816

AN:

67990

Other (OTH)

AF:

0.371

AC:

783

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1334

2668

4003

5337

6671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.305

Hom.:

4056

Bravo

AF:

0.448

Asia WGS

AF:

0.283

AC:

982

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency, common variable, 4

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.0

(source)

DANN

Benign

0.52

PhyloP100

0.68

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over