17-16939458-CTCA-C

Variant names:

• chr17-16939458-CTCA-C
• rs150068036
• NM_012452.3:c.*86_*88delTGA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_012452.3(TNFRSF13B):​c.*86_*88delTGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,444,368 control chromosomes in the GnomAD database, including 1,847 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (206 hom., cov: 29)
  • Exomes 𝑓: 0.039 (1641 hom.)
• Consequence: TNFRSF13B NM_012452.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0260
• Publications: 4 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 -16 ACMG points.

• BP6: Variant 17-16939458-CTCA-C is Benign according to our data. Variant chr17-16939458-CTCA-C is described in ClinVar as [Benign]. Clinvar id is 36880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.*86_*88delTGA		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.*86_*88delTGA		3_prime_UTR_variant	Exon 5 of 5	1	NM_012452.3	ENSP00000261652.2

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5790 AN: 151350 Hom.: 206 Cov.: 29

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0412

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0371

GnomAD4 exome AF: 0.0390 AC: 50387 AN: 1292900 Hom.: 1641 AF XY: 0.0404 AC XY: 25599 AN XY: 634112

African (AFR) AF: 0.0303 AC: 905 AN: 29850

American (AMR) AF: 0.0634 AC: 2135 AN: 33654

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 456 AN: 22042

East Asian (EAS) AF: 0.193 AC: 6741 AN: 34928

South Asian (SAS) AF: 0.0784 AC: 5513 AN: 70358

European-Finnish (FIN) AF: 0.0297 AC: 1204 AN: 40518

Middle Eastern (MID) AF: 0.0639 AC: 341 AN: 5336

European-Non Finnish (NFE) AF: 0.0308 AC: 30906 AN: 1001886

Other (OTH) AF: 0.0402 AC: 2186 AN: 54328

GnomAD4 genome AF: 0.0383 AC: 5794 AN: 151468 Hom.: 206 Cov.: 29 AF XY: 0.0388 AC XY: 2875 AN XY: 74008

African (AFR) AF: 0.0305 AC: 1260 AN: 41288

American (AMR) AF: 0.0410 AC: 625 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.190 AC: 962 AN: 5052

South Asian (SAS) AF: 0.0816 AC: 389 AN: 4770

European-Finnish (FIN) AF: 0.0272 AC: 287 AN: 10546

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0312 AC: 2113 AN: 67812

Other (OTH) AF: 0.0371 AC: 78 AN: 2100

Alfa AF: 0.0322 Hom.: 5

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Apr 26, 2022

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: TNFRSF13B c.*86_*88delTGA is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.04 in 31156 control chromosomes in the gnomAD database, including 49 homozygotes. The observed variant frequency is approximately 14076 fold of the estimated maximal expected allele frequency for a pathogenic variant in TNFRSF13B causing Common Variable Immunodeficiency phenotype (2.9e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.*86_*88delTGA in individuals affected with Common Variable Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -

Immunodeficiency, common variable, 2 Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.026
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: rs150068036; hg19: chr17-16842772;