rs1299671576

Variant names:

• chr22-41926337-TC-T
• rs1299671576
• NM_052945.4:c.137-7delG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_052945.4(TNFRSF13C):​c.137-7delG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,298,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: TNFRSF13C NM_052945.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.929
• 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):

• 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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 22-41926337-TC-T is Benign according to our data. Variant chr22-41926337-TC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 471472.Status of the report is criteria_provided_single_submitter, 1 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13C	NM_052945.4	MANE Select	c.137-7delG		splice_region intron	N/A	NP_443177.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13C	ENST00000291232.5	TSL:1 MANE Select	c.137-7delG		splice_region intron	N/A	ENSP00000291232.3

Frequencies

GnomAD3 genomes AF: 0.0000407 AC: 6 AN: 147548 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000750

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000233 AC: 1 AN: 43010 AF XY: 0.0000384

Gnomad AFR exome AF: 0.00

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: 0.0000555

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000573 AC: 66 AN: 1151126 Hom.: 0 Cov.: 33 AF XY: 0.0000532 AC XY: 30 AN XY: 563866

African (AFR) AF: 0.0000464 AC: 1 AN: 21540

American (AMR) AF: 0.00 AC: 0 AN: 12038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16292

East Asian (EAS) AF: 0.00 AC: 0 AN: 18414

South Asian (SAS) AF: 0.00 AC: 0 AN: 58514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3144

European-Non Finnish (NFE) AF: 0.0000668 AC: 64 AN: 957860

Other (OTH) AF: 0.0000224 AC: 1 AN: 44734

GnomAD4 genome AF: 0.0000407 AC: 6 AN: 147548 Hom.: 0 Cov.: 32 AF XY: 0.0000417 AC XY: 3 AN XY: 71896

African (AFR) AF: 0.0000247 AC: 1 AN: 40424

American (AMR) AF: 0.00 AC: 0 AN: 14896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 4772

South Asian (SAS) AF: 0.00 AC: 0 AN: 4400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000750 AC: 5 AN: 66680

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency, common variable, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism

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: rs1299671576; hg19: chr22-42322341;