rs235249

Variant names:

• chr1-12198174-T-C
• rs235249
• NM_001066.3:c.900+3556T>C

Variant summary

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

The NM_001066.3(TNFRSF1B):​c.900+3556T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 149,440 control chromosomes in the GnomAD database, including 4,145 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 0.23 (4145 hom., cov: 29)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 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.900+3556T>C		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.900+3556T>C		intron	N/A	ENSP00000365435.3
	TNFRSF1B	ENST00000492361.1	TSL:1	n.889+3556T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.233 AC: 34831 AN: 149358 Hom.: 4127 Cov.: 29

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.233 AC: 34893 AN: 149440 Hom.: 4145 Cov.: 29 AF XY: 0.231 AC XY: 16774 AN XY: 72646

African (AFR) AF: 0.255 AC: 10337 AN: 40554

American (AMR) AF: 0.154 AC: 2307 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3462

East Asian (EAS) AF: 0.167 AC: 847 AN: 5074

South Asian (SAS) AF: 0.267 AC: 1262 AN: 4732

European-Finnish (FIN) AF: 0.230 AC: 2229 AN: 9672

Middle Eastern (MID) AF: 0.269 AC: 77 AN: 286

European-Non Finnish (NFE) AF: 0.240 AC: 16249 AN: 67652

Other (OTH) AF: 0.229 AC: 474 AN: 2072

Alfa AF: 0.238 Hom.: 2296

Bravo AF: 0.227

Asia WGS AF: 0.213 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs235249; hg19: chr1-12258231; COSMIC: COSV66163951;