17-16939936-A-C

Position:

• chr17-16939936-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012452.3(TNFRSF13B):​c.632-139T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,241,898 control chromosomes in the GnomAD database, including 38,900 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 0.19 (3373 hom., cov: 33)
  • Exomes 𝑓: 0.25 (35527 hom.)
• Consequence: TNFRSF13B NM_012452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.632-139T>G		intron_variant		ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.632-139T>G		intron_variant		1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28561 AN: 152094 Hom.: 3375 Cov.: 33

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.247 AC: 269313 AN: 1089686 Hom.: 35527 Cov.: 15 AF XY: 0.245 AC XY: 130918 AN XY: 533878

Gnomad4 AFR exome AF: 0.0479

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.000595

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.188 AC: 28555 AN: 152212 Hom.: 3373 Cov.: 33 AF XY: 0.182 AC XY: 13578 AN XY: 74432

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.213

Alfa AF: 0.132 Hom.: 245

Bravo AF: 0.182

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11652843; hg19: chr17-16843250; COSMIC: COSV55430920; COSMIC: COSV55430920;