17-16939133-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012452.3(TNFRSF13B):c.*414G>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 0.0828 in 166,062 control chromosomes in the GnomAD database, including 922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (871 hom., cov: 31)
  • Exomes 𝑓: 0.062 (51 hom.)
• Consequence: TNFRSF13B NM_012452.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.63

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-16939133-C-T is Benign according to our data. Variant chr17-16939133-C-T is described in ClinVar as [Benign]. Clinvar id is 322018.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF13B	NM_012452.3	c.*414G>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.*414G>A		3_prime_UTR_variant	5/5	1	NM_012452.3	P2

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12888 AN: 151966 Hom.: 874 Cov.: 31

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.0620 AC: 866 AN: 13978 Hom.: 51 Cov.: 0 AF XY: 0.0638 AC XY: 448 AN XY: 7024

Gnomad4 AFR exome AF: 0.0598

Gnomad4 AMR exome AF: 0.0438

Gnomad4 ASJ exome AF: 0.0311

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.0921

Gnomad4 FIN exome AF: 0.0448

Gnomad4 NFE exome AF: 0.0481

Gnomad4 OTH exome AF: 0.0659

GnomAD4 genome AF: 0.0847 AC: 12887 AN: 152084 Hom.: 871 Cov.: 31 AF XY: 0.0891 AC XY: 6621 AN XY: 74344

Gnomad4 AFR AF: 0.0839

Gnomad4 AMR AF: 0.0946

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0727

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0644 Hom.: 111

Bravo AF: 0.0850

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Common Variable Immune Deficiency, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.12
Dann	Benign	0.42

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: rs55701306; hg19: chr17-16842447;