22-41925357-C-G

Variant names:

• chr22-41925357-C-G
• rs375349302
• NM_052945.4:c.*10G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_052945.4(TNFRSF13C):​c.*10G>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 0.0000872 in 1,594,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: TNFRSF13C NM_052945.4 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0660
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 22-41925357-C-G is Benign according to our data. Variant chr22-41925357-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3042050.Status of the report is no_assertion_criteria_provided, 0 stars.

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.*10G>C		3_prime_UTR	Exon 3 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.*10G>C		3_prime_UTR	Exon 3 of 3	ENSP00000291232.3	Q96RJ3-1
	TNFRSF13C	ENST00000898406.1		c.*10G>C		3_prime_UTR	Exon 3 of 3	ENSP00000568465.1

Frequencies

GnomAD3 genomes AF: 0.0000725 AC: 11 AN: 151804 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000297 AC: 7 AN: 235932 AF XY: 0.0000310

Gnomad AFR exome AF: 0.0000671

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000556

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000887 AC: 128 AN: 1442482 Hom.: 0 Cov.: 31 AF XY: 0.0000782 AC XY: 56 AN XY: 716168

African (AFR) AF: 0.0000301 AC: 1 AN: 33228

American (AMR) AF: 0.0000454 AC: 2 AN: 44038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.00 AC: 0 AN: 85696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4550

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1105420

Other (OTH) AF: 0.0000670 AC: 4 AN: 59658

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 151922 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74242

African (AFR) AF: 0.0000241 AC: 1 AN: 41416

American (AMR) AF: 0.0000656 AC: 1 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67962

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000604

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TNFRSF13C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.4
DANN	Benign	0.69
PhyloP100		-0.066

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

Other links and lift over

dbSNP: rs375349302; hg19: chr22-42321361;