rs5746016

chr1-12190922-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.179-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 1,603,760 control chromosomes in the GnomAD database, including 1,979 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (149 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1830 hom.)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF1B	NM_001066.3	c.179-35C>T		intron_variant		ENST00000376259.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.179-35C>T		intron_variant		1	NM_001066.3	P1
TNFRSF1B	ENST00000536782.2	c.179-35C>T		intron_variant		1
TNFRSF1B	ENST00000492361.1	n.168-35C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6308 AN: 151998 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0297

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0407

GnomAD3 exomes AF: 0.0432 AC: 10689 AN: 247478 Hom.: 287 AF XY: 0.0436 AC XY: 5823 AN XY: 133664

Gnomad AFR exome AF: 0.0261

Gnomad AMR exome AF: 0.0202

Gnomad ASJ exome AF: 0.0600

Gnomad EAS exome AF: 0.000599

Gnomad SAS exome AF: 0.0302

Gnomad FIN exome AF: 0.0811

Gnomad NFE exome AF: 0.0542

Gnomad OTH exome AF: 0.0480

GnomAD4 exome AF: 0.0477 AC: 69226 AN: 1451644 Hom.: 1830 Cov.: 31 AF XY: 0.0471 AC XY: 33945 AN XY: 720506

Gnomad4 AFR exome AF: 0.0281

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0588

Gnomad4 EAS exome AF: 0.000329

Gnomad4 SAS exome AF: 0.0278

Gnomad4 FIN exome AF: 0.0844

Gnomad4 NFE exome AF: 0.0509

Gnomad4 OTH exome AF: 0.0424

GnomAD4 genome AF: 0.0414 AC: 6304 AN: 152116 Hom.: 149 Cov.: 32 AF XY: 0.0419 AC XY: 3113 AN XY: 74362

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.0503

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0479 Hom.: 122

Bravo AF: 0.0364

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.1
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs5746016; hg19: chr1-12250979;