rs12603708

Variant names:

• chr17-16943799-G-A
• rs12603708
• NM_012452.3:c.446-3288C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-16943799-G-A
• chr17-16943799-G-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.446-3288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,054 control chromosomes in the GnomAD database, including 7,258 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 0.28 (7258 hom., cov: 32)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 7 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), Laboratory for Molecular Medicine, ClinGen, G2P, Ambry Genetics
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.446-3288C>T		intron_variant	Intron 3 of 4	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.446-3288C>T		intron_variant	Intron 3 of 4	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41815 AN: 151936 Hom.: 7233 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.276 AC: 41895 AN: 152054 Hom.: 7258 Cov.: 32 AF XY: 0.280 AC XY: 20780 AN XY: 74326

African (AFR) AF: 0.424 AC: 17589 AN: 41458

American (AMR) AF: 0.270 AC: 4126 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3725 AN: 5164

South Asian (SAS) AF: 0.369 AC: 1777 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1665 AN: 10588

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11494 AN: 67962

Other (OTH) AF: 0.243 AC: 512 AN: 2108

Alfa AF: 0.214 Hom.: 11512

Bravo AF: 0.288

Asia WGS AF: 0.520 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.84
DANN	Benign	0.37
PhyloP100		-2.0
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: rs12603708; hg19: chr17-16847113; COSMIC: COSV55427209; COSMIC: COSV55427209;