rs1061624

Positions:

• chr1-12207208-A-G
• chr1-12207208-A-T

Variant summary

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

The NM_001066.3(TNFRSF1B):​c.*188A>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 0.515 in 537,976 control chromosomes in the GnomAD database, including 73,598 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 0.48 (18701 hom., cov: 32)
  • Exomes 𝑓: 0.53 (54897 hom.)
• Consequence: TNFRSF1B NM_001066.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.727

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3	c.*188A>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.*188A>G		3_prime_UTR_variant	10/10	1	NM_001066.3	ENSP00000365435.3
TNFRSF1B	ENST00000492361.1	n.1563A>G		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73596 AN: 151978 Hom.: 18690 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.528 AC: 203666 AN: 385880 Hom.: 54897 Cov.: 6 AF XY: 0.526 AC XY: 103461 AN XY: 196520

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.647

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.512

GnomAD4 genome AF: 0.484 AC: 73613 AN: 152096 Hom.: 18701 Cov.: 32 AF XY: 0.491 AC XY: 36484 AN XY: 74342

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.499

Alfa AF: 0.541 Hom.: 16042

Bravo AF: 0.471

Asia WGS AF: 0.430 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.48

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: rs1061624; hg19: chr1-12267265; COSMIC: COSV66164855;