rs3397

chr1-12207235-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001066.3(TNFRSF1B):c.*215C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 473,266 control chromosomes in the GnomAD database, including 81,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.51 (22516 hom., cov: 33)
  • Exomes 𝑓: 0.60 (59315 hom.)
• Consequence: TNFRSF1B NM_001066.3 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:3
• Conservation: PhyloP100: -0.400

Genes affected

TNFRSF1B (HGNC:11917): (TNF receptor superfamily member 1B) The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF1B	NM_001066.3	c.*215C>T		3_prime_UTR_variant	10/10	ENST00000376259.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.*215C>T		3_prime_UTR_variant	10/10	1	NM_001066.3	P1
TNFRSF1B	ENST00000492361.1	n.1590C>T		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77531 AN: 152072 Hom.: 22512 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.599 AC: 192198 AN: 321076 Hom.: 59315 Cov.: 5 AF XY: 0.600 AC XY: 98421 AN XY: 163988

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.703

Gnomad4 ASJ exome AF: 0.670

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.510 AC: 77556 AN: 152190 Hom.: 22516 Cov.: 33 AF XY: 0.511 AC XY: 38008 AN XY: 74394

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.531

Alfa AF: 0.583 Hom.: 8581

Bravo AF: 0.506

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: no assertion criteria provided

Submissions by phenotype

Associated with severe COVID-19 disease Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 01, 2023

- -

Susceptibility to severe coronavirus disease (COVID-19) Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Feb 09, 2021

- -

Susceptibility to severe coronavirus disease (COVID-19) due to high plasma levels of TNF, TNFR, and/or TNFR3 Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Aug 07, 2021

Differences in PaO2/FiO2 levels in patients with severe COVID-19 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.5
Dann	Benign	0.86

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: rs3397; hg19: chr1-12267292; COSMIC: COSV66164003;