rs5745994

Variant names:

• chr1-12187071-C-T
• rs5745994
• NM_001066.3:c.79-1725C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001066.3(TNFRSF1B):​c.79-1725C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 152,100 control chromosomes in the GnomAD database, including 46 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 0.022 (46 hom., cov: 32)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 2 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=-0.94).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0221 (3368/152100) while in subpopulation NFE AF = 0.0349 (2371/67976). AF 95% confidence interval is 0.0337. There are 46 homozygotes in GnomAd4. There are 1513 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3	c.79-1725C>T		intron_variant	Intron 1 of 9	ENST00000376259.7	NP_001057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.79-1725C>T		intron_variant	Intron 1 of 9	1	NM_001066.3	ENSP00000365435.3
TNFRSF1B	ENST00000536782.2	c.79-1725C>T		intron_variant	Intron 1 of 4	1		ENSP00000440425.1
TNFRSF1B	ENST00000492361.1	n.168-3886C>T		intron_variant	Intron 1 of 8	1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3372 AN: 152002 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00655

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0221 AC: 3368 AN: 152100 Hom.: 46 Cov.: 32 AF XY: 0.0204 AC XY: 1513 AN XY: 74342

African (AFR) AF: 0.00653 AC: 271 AN: 41490

American (AMR) AF: 0.0124 AC: 189 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 88 AN: 3472

East Asian (EAS) AF: 0.0206 AC: 107 AN: 5182

South Asian (SAS) AF: 0.0229 AC: 110 AN: 4808

European-Finnish (FIN) AF: 0.0142 AC: 150 AN: 10564

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0349 AC: 2371 AN: 67976

Other (OTH) AF: 0.0204 AC: 43 AN: 2106

Alfa AF: 0.0236 Hom.: 8

Bravo AF: 0.0212

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		-0.039
Mutation Taster		=100/0	polymorphism

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: rs5745994; hg19: chr1-12247128; COSMIC: COSV66163851; COSMIC: COSV66163851;