NM_012452.3:c.446-1342T>C

Variant names:

• chr17-16941853-A-G
• rs4792800
• NM_012452.3:c.446-1342T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012452.3(TNFRSF13B):​c.446-1342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,132 control chromosomes in the GnomAD database, including 1,454 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1454 hom., cov: 32)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 27 publications found

Genes affected

TNFRSF13B (HGNC:18153): (TNF receptor superfamily member 13B) The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

TNFRSF13B Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, G2P, ClinGen
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000307457 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012452.3. 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
	TNFRSF13B	NM_012452.3	MANE Select	c.446-1342T>C		intron	N/A	NP_036584.1	O14836-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF13B	ENST00000261652.7	TSL:1 MANE Select	c.446-1342T>C		intron	N/A	ENSP00000261652.2	O14836-1
	TNFRSF13B	ENST00000583789.1	TSL:1	c.308-1342T>C		intron	N/A	ENSP00000462952.1	O14836-2
	TNFRSF13B	ENST00000579315.5	TSL:3	c.445+6885T>C		intron	N/A	ENSP00000464069.1	J3QR67

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19436 AN: 152014 Hom.: 1457 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 19431 AN: 152132 Hom.: 1454 Cov.: 32 AF XY: 0.130 AC XY: 9702 AN XY: 74368

African (AFR) AF: 0.126 AC: 5235 AN: 41496

American (AMR) AF: 0.127 AC: 1944 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2118 AN: 5162

South Asian (SAS) AF: 0.160 AC: 770 AN: 4814

European-Finnish (FIN) AF: 0.0991 AC: 1049 AN: 10590

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7376 AN: 67984

Other (OTH) AF: 0.115 AC: 243 AN: 2108

Alfa AF: 0.119 Hom.: 4789

Bravo AF: 0.129

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.59
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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: rs4792800; hg19: chr17-16845167; COSMIC: COSV55427160; COSMIC: COSV55427160;