rs7290134

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

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

Conservation

PhyloP100: 0.681
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]

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 (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 id 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/exons MANE Protein UniProt
TNFRSF13CNM_052945.4 linkuse as main transcriptc.*120T>C 3_prime_UTR_variant 3/3 ENST00000291232.5 NP_443177.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNFRSF13CENST00000291232.5 linkuse as main transcriptc.*120T>C 3_prime_UTR_variant 3/31 NM_052945.4 ENSP00000291232 P1Q96RJ3-1

Frequencies

GnomAD3 genomes
AF:
0.408
AC:
62078
AN:
152016
Hom.:
18175
Cov.:
32
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.:
12
AF XY:
0.254
AC XY:
120678
AN XY:
475028
show subpopulations
Gnomad4 AFR exome
AF:
0.840
Gnomad4 AMR exome
AF:
0.547
Gnomad4 ASJ exome
AF:
0.283
Gnomad4 EAS exome
AF:
0.105
Gnomad4 SAS exome
AF:
0.348
Gnomad4 FIN exome
AF:
0.204
Gnomad4 NFE exome
AF:
0.224
Gnomad4 OTH exome
AF:
0.291
GnomAD4 genome
AF:
0.409
AC:
62198
AN:
152134
Hom.:
18242
Cov.:
32
AF XY:
0.405
AC XY:
30145
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.818
Gnomad4 AMR
AF:
0.462
Gnomad4 ASJ
AF:
0.281
Gnomad4 EAS
AF:
0.117
Gnomad4 SAS
AF:
0.358
Gnomad4 FIN
AF:
0.195
Gnomad4 NFE
AF:
0.218
Gnomad4 OTH
AF:
0.371
Alfa
AF:
0.304
Hom.:
2346
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
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Immunodeficiency, common variable, 4 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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
DANN
Benign
0.52

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

LitVar

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

Other links and lift over

dbSNP: rs7290134; hg19: chr22-42321251; COSMIC: COSV52170161; COSMIC: COSV52170161; API