17-16939458-CTCA-C

Position:

• chr17-16939458-CTCA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_012452.3(TNFRSF13B):​c.*86_*88del 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

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 -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/exons	MANE	Protein	UniProt
TNFRSF13B	NM_012452.3	c.*86_*88del		3_prime_UTR_variant	5/5	ENST00000261652.7	NP_036584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF13B	ENST00000261652.7	c.*86_*88del		3_prime_UTR_variant	5/5	1	NM_012452.3	ENSP00000261652	P2

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

Gnomad4 AFR exome AF: 0.0303

Gnomad4 AMR exome AF: 0.0634

Gnomad4 ASJ exome AF: 0.0207

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.0784

Gnomad4 FIN exome AF: 0.0297

Gnomad4 NFE exome AF: 0.0308

Gnomad4 OTH exome AF: 0.0402

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

Gnomad4 AFR AF: 0.0305

Gnomad4 AMR AF: 0.0410

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0371

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

Benign, criteria provided, single submitter

clinical testing

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

Apr 26, 2022

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs150068036; hg19: chr17-16842772;