17-16939133-C-T

Variant names:

• chr17-16939133-C-T
• rs55701306
• NM_012452.3:c.*414G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.63
• Publications: 8 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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.*414G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.*414G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_012452.3	ENSP00000261652.2

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

African (AFR) AF: 0.0598 AC: 25 AN: 418

American (AMR) AF: 0.0438 AC: 22 AN: 502

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 17 AN: 546

East Asian (EAS) AF: 0.330 AC: 184 AN: 558

South Asian (SAS) AF: 0.0921 AC: 58 AN: 630

European-Finnish (FIN) AF: 0.0448 AC: 35 AN: 782

Middle Eastern (MID) AF: 0.0741 AC: 4 AN: 54

European-Non Finnish (NFE) AF: 0.0481 AC: 461 AN: 9578

Other (OTH) AF: 0.0659 AC: 60 AN: 910

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

African (AFR) AF: 0.0839 AC: 3479 AN: 41478

American (AMR) AF: 0.0946 AC: 1447 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2104 AN: 5148

South Asian (SAS) AF: 0.135 AC: 650 AN: 4798

European-Finnish (FIN) AF: 0.0727 AC: 770 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0593 AC: 4035 AN: 67990

Other (OTH) AF: 0.0714 AC: 151 AN: 2114

Alfa AF: 0.0660 Hom.: 256

Bravo AF: 0.0850

Asia WGS AF: 0.249 AC: 863 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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.42
PhyloP100		-3.6
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: rs55701306; hg19: chr17-16842447;