rs5030792

Positions:

• chr1-12207213-T-G

Variant summary

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

The NM_001066.3(TNFRSF1B):​c.*193T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 518,788 control chromosomes in the GnomAD database, including 548 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 0.033 (126 hom., cov: 33)
  • Exomes 𝑓: 0.045 (422 hom.)
• Consequence: TNFRSF1B NM_001066.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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]

TNFRSF1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3	c.*193T>G		3_prime_UTR_variant	10/10	ENST00000376259.7	NP_001057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.*193T>G		3_prime_UTR_variant	10/10	1	NM_001066.3	ENSP00000365435.3
TNFRSF1B	ENST00000492361.1	n.1568T>G		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4969 AN: 152126 Hom.: 126 Cov.: 33

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0432

GnomAD4 exome AF: 0.0446 AC: 16348 AN: 366544 Hom.: 422 Cov.: 5 AF XY: 0.0445 AC XY: 8319 AN XY: 186806

Gnomad4 AFR exome AF: 0.00978

Gnomad4 AMR exome AF: 0.0325

Gnomad4 ASJ exome AF: 0.0755

Gnomad4 EAS exome AF: 0.0000388

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.0214

Gnomad4 NFE exome AF: 0.0541

Gnomad4 OTH exome AF: 0.0445

GnomAD4 genome AF: 0.0327 AC: 4972 AN: 152244 Hom.: 126 Cov.: 33 AF XY: 0.0306 AC XY: 2281 AN XY: 74438

Gnomad4 AFR AF: 0.00878

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0127

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.0504

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0410 Hom.: 18

Bravo AF: 0.0343

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.66

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: rs5030792; hg19: chr1-12267270;