rs5746051

Variant names:

• chr1-12201915-A-G
• rs5746051
• NM_001066.3:c.901-52A>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.901-52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,524,892 control chromosomes in the GnomAD database, including 25,056 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 0.14 (1756 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23300 hom.)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 21 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 = 0.212 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF1B	NM_001066.3	MANE Select	c.901-52A>G		intron	N/A	NP_001057.1	P20333-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF1B	ENST00000376259.7	TSL:1 MANE Select	c.901-52A>G		intron	N/A	ENSP00000365435.3	P20333-1
	TNFRSF1B	ENST00000492361.1	TSL:1	n.890-52A>G		intron	N/A
	TNFRSF1B	ENST00000941756.1		c.1012-52A>G		intron	N/A	ENSP00000611815.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21241 AN: 152072 Hom.: 1753 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.181 AC: 247923 AN: 1372700 Hom.: 23300 Cov.: 33 AF XY: 0.183 AC XY: 122646 AN XY: 671460

African (AFR) AF: 0.0539 AC: 1684 AN: 31238

American (AMR) AF: 0.0949 AC: 3285 AN: 34608

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 4208 AN: 23994

East Asian (EAS) AF: 0.146 AC: 5199 AN: 35696

South Asian (SAS) AF: 0.227 AC: 17586 AN: 77640

European-Finnish (FIN) AF: 0.147 AC: 7101 AN: 48258

Middle Eastern (MID) AF: 0.209 AC: 1100 AN: 5272

European-Non Finnish (NFE) AF: 0.187 AC: 197765 AN: 1059428

Other (OTH) AF: 0.177 AC: 9995 AN: 56566

GnomAD4 genome AF: 0.140 AC: 21261 AN: 152192 Hom.: 1756 Cov.: 32 AF XY: 0.139 AC XY: 10375 AN XY: 74422

African (AFR) AF: 0.0572 AC: 2376 AN: 41550

American (AMR) AF: 0.111 AC: 1694 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3470

East Asian (EAS) AF: 0.165 AC: 856 AN: 5182

South Asian (SAS) AF: 0.223 AC: 1077 AN: 4822

European-Finnish (FIN) AF: 0.151 AC: 1606 AN: 10608

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12564 AN: 67962

Other (OTH) AF: 0.154 AC: 326 AN: 2114

Alfa AF: 0.158 Hom.: 1516

Bravo AF: 0.132

Asia WGS AF: 0.175 AC: 609 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	2.2
DANN	Benign	0.28
PhyloP100		-0.095
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: rs5746051; hg19: chr1-12261972; COSMIC: COSV66163968;