22-41926714-G-T

Variant names:

• chr22-41926714-G-T
• rs373828157
• NM_052945.4:c.60C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052945.4(TNFRSF13C):​c.60C>A​(p.Val20Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000771 in 1,296,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V20V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: TNFRSF13C NM_052945.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.60C>A	p.Val20Val	synonymous	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.60C>A	p.Val20Val	synonymous	Exon 1 of 3	ENSP00000291232.3	Q96RJ3-1
	TNFRSF13C	ENST00000898406.1		c.60C>A	p.Val20Val	synonymous	Exon 1 of 3	ENSP00000568465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.71e-7 AC: 1 AN: 1296834 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 638154

African (AFR) AF: 0.0000382 AC: 1 AN: 26174

American (AMR) AF: 0.00 AC: 0 AN: 23930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22512

East Asian (EAS) AF: 0.00 AC: 0 AN: 27900

South Asian (SAS) AF: 0.00 AC: 0 AN: 69218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3852

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1037226

Other (OTH) AF: 0.00 AC: 0 AN: 53626

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.83
PhyloP100		-0.17
PromoterAI		-0.13	Neutral

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: rs373828157; hg19: chr22-42322718;