17-16939374-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012452.3(TNFRSF13B):c.*173G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 738,034 control chromosomes in the GnomAD database, including 49,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11763 hom., cov: 28)
  • Exomes 𝑓: 0.35 (38099 hom.)
• Consequence: TNFRSF13B NM_012452.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.56

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-16939374-C-T is Benign according to our data. Variant chr17-16939374-C-T is described in ClinVar as [Benign]. Clinvar id is 322022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF13B	NM_012452.3	c.*173G>A		3_prime_UTR_variant	5/5	ENST00000261652.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.*173G>A		3_prime_UTR_variant	5/5	1	NM_012452.3	P2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 58707 AN: 150492 Hom.: 11741 Cov.: 28

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.350 AC: 205332 AN: 587424 Hom.: 38099 Cov.: 8 AF XY: 0.351 AC XY: 104426 AN XY: 297154

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.390 AC: 58780 AN: 150610 Hom.: 11763 Cov.: 28 AF XY: 0.391 AC XY: 28748 AN XY: 73508

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.369

Alfa AF: 0.369 Hom.: 1388

Bravo AF: 0.404

Asia WGS AF: 0.444 AC: 1545 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Common Variable Immune Deficiency, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.39
Dann	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs56153623; hg19: chr17-16842688; COSMIC: COSV55425237; COSMIC: COSV55425237;