rs5745993

Variant names:

• chr1-12186951-C-G
• rs5745993
• NM_001066.3:c.79-1845C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001066.3(TNFRSF1B):​c.79-1845C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,198 control chromosomes in the GnomAD database, including 1,315 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 0.12 (1315 hom., cov: 32)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001066.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF1B	NM_001066.3	MANE Select	c.79-1845C>G		intron	N/A	NP_001057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF1B	ENST00000376259.7	TSL:1 MANE Select	c.79-1845C>G		intron	N/A	ENSP00000365435.3
	TNFRSF1B	ENST00000536782.2	TSL:1	c.79-1845C>G		intron	N/A	ENSP00000440425.1
	TNFRSF1B	ENST00000492361.1	TSL:1	n.168-4006C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17954 AN: 152080 Hom.: 1316 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.0705

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.118 AC: 17954 AN: 152198 Hom.: 1315 Cov.: 32 AF XY: 0.118 AC XY: 8780 AN XY: 74404

African (AFR) AF: 0.0387 AC: 1608 AN: 41538

American (AMR) AF: 0.0978 AC: 1494 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 623 AN: 3470

East Asian (EAS) AF: 0.133 AC: 688 AN: 5182

South Asian (SAS) AF: 0.203 AC: 977 AN: 4820

European-Finnish (FIN) AF: 0.115 AC: 1216 AN: 10602

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10964 AN: 67996

Other (OTH) AF: 0.126 AC: 267 AN: 2112

Alfa AF: 0.131 Hom.: 205

Bravo AF: 0.113

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.71
PhyloP100		-0.19
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: rs5745993; hg19: chr1-12247008;