rs5746016

Variant names:

• chr1-12190922-C-T
• rs5746016
• NM_001066.3:c.179-35C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3	c.179-35C>T		intron_variant	Intron 2 of 9	ENST00000376259.7	NP_001057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.179-35C>T		intron_variant	Intron 2 of 9	1	NM_001066.3	ENSP00000365435.3
TNFRSF1B	ENST00000536782.2	c.179-35C>T		intron_variant	Intron 2 of 4	1		ENSP00000440425.1
TNFRSF1B	ENST00000492361.1	n.168-35C>T		intron_variant	Intron 1 of 8	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

GnomAD2 exomes AF: 0.0432 AC: 10689 AN: 247478 AF XY: 0.0436

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 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

African (AFR) AF: 0.0281 AC: 936 AN: 33290

American (AMR) AF: 0.0212 AC: 939 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 1517 AN: 25778

East Asian (EAS) AF: 0.000329 AC: 13 AN: 39502

South Asian (SAS) AF: 0.0278 AC: 2383 AN: 85692

European-Finnish (FIN) AF: 0.0844 AC: 4477 AN: 53068

Middle Eastern (MID) AF: 0.0379 AC: 217 AN: 5730

European-Non Finnish (NFE) AF: 0.0509 AC: 56205 AN: 1104500

Other (OTH) AF: 0.0424 AC: 2539 AN: 59854

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

African (AFR) AF: 0.0256 AC: 1061 AN: 41500

American (AMR) AF: 0.0265 AC: 405 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0293 AC: 141 AN: 4818

European-Finnish (FIN) AF: 0.0837 AC: 885 AN: 10572

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0503 AC: 3421 AN: 67994

Other (OTH) AF: 0.0402 AC: 85 AN: 2112

Alfa AF: 0.0483 Hom.: 162

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
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5746016; hg19: chr1-12250979;