rs472093

chr1-12191134-T-A

Variant summary

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

The NM_001066.3(TNFRSF1B):c.307+49T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,591,908 control chromosomes in the GnomAD database, including 25,437 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 0.15 (1806 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23631 hom.)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF1B	NM_001066.3	c.307+49T>A		intron_variant		ENST00000376259.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.307+49T>A		intron_variant		1	NM_001066.3	P1
TNFRSF1B	ENST00000536782.2	c.307+49T>A		intron_variant		1
TNFRSF1B	ENST00000492361.1	n.296+49T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22124 AN: 152082 Hom.: 1801 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.153

GnomAD3 exomes AF: 0.167 AC: 40276 AN: 241524 Hom.: 3623 AF XY: 0.174 AC XY: 22759 AN XY: 130832

Gnomad AFR exome AF: 0.0830

Gnomad AMR exome AF: 0.0982

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.137

Gnomad SAS exome AF: 0.232

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.178 AC: 255907 AN: 1439708 Hom.: 23631 Cov.: 31 AF XY: 0.180 AC XY: 128532 AN XY: 713382

Gnomad4 AFR exome AF: 0.0832

Gnomad4 AMR exome AF: 0.0999

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.146 AC: 22156 AN: 152200 Hom.: 1806 Cov.: 32 AF XY: 0.145 AC XY: 10821 AN XY: 74420

Gnomad4 AFR AF: 0.0817

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.157

Alfa AF: 0.169 Hom.: 498

Bravo AF: 0.139

Asia WGS AF: 0.157 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.031
Dann	Benign	0.53

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: rs472093; hg19: chr1-12251191; COSMIC: COSV66164361; COSMIC: COSV66164361;