rs35062843

Positions:

• chr17-16948892-A-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012452.3(TNFRSF13B):​c.291T>G​(p.Pro97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,614,174 control chromosomes in the GnomAD database, including 1,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (125 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1554 hom.)
• Consequence: TNFRSF13B NM_012452.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.313

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-16948892-A-C is Benign according to our data. Variant chr17-16948892-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 260258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-16948892-A-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.313 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.291T>G	p.Pro97=	synonymous_variant	3/5	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.291T>G	p.Pro97=	synonymous_variant	3/5	1	NM_012452.3	ENSP00000261652	P2

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5561 AN: 152176 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0483

GnomAD3 exomes AF: 0.0415 AC: 10448 AN: 251480 Hom.: 324 AF XY: 0.0443 AC XY: 6018 AN XY: 135910

Gnomad AFR exome AF: 0.0239

Gnomad AMR exome AF: 0.0383

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00799

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.0375

Gnomad NFE exome AF: 0.0373

Gnomad OTH exome AF: 0.0401

GnomAD4 exome AF: 0.0417 AC: 61000 AN: 1461880 Hom.: 1554 Cov.: 36 AF XY: 0.0434 AC XY: 31551 AN XY: 727240

Gnomad4 AFR exome AF: 0.0251

Gnomad4 AMR exome AF: 0.0411

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.00851

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.0385

Gnomad4 NFE exome AF: 0.0398

Gnomad4 OTH exome AF: 0.0418

GnomAD4 genome AF: 0.0366 AC: 5572 AN: 152294 Hom.: 125 Cov.: 32 AF XY: 0.0375 AC XY: 2795 AN XY: 74480

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0551

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0331

Gnomad4 NFE AF: 0.0383

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.0350 Hom.: 54

Bravo AF: 0.0342

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 13, 2018	- -

Immunodeficiency, common variable, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Common Variable Immune Deficiency, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.56

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: rs35062843; hg19: chr17-16852206;