1-12172749-T-C

Variant names:

• chr1-12172749-T-C
• rs496888
• NM_001066.3:c.78+5580T>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.78+5580T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,158 control chromosomes in the GnomAD database, including 7,827 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 0.32 (7827 hom., cov: 33)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.72
• Publications: 27 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 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.78+5580T>C		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.78+5580T>C		intron	N/A	ENSP00000365435.3	P20333-1
	TNFRSF1B	ENST00000536782.2	TSL:1	c.78+5580T>C		intron	N/A	ENSP00000440425.1	B5A977
	TNFRSF1B	ENST00000492361.1	TSL:1	n.167+5580T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47892 AN: 152040 Hom.: 7810 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.315 AC: 47964 AN: 152158 Hom.: 7827 Cov.: 33 AF XY: 0.314 AC XY: 23388 AN XY: 74392

African (AFR) AF: 0.310 AC: 12862 AN: 41506

American (AMR) AF: 0.442 AC: 6759 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1042 AN: 5178

South Asian (SAS) AF: 0.185 AC: 895 AN: 4832

European-Finnish (FIN) AF: 0.340 AC: 3603 AN: 10586

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20894 AN: 67978

Other (OTH) AF: 0.310 AC: 656 AN: 2114

Alfa AF: 0.305 Hom.: 13975

Bravo AF: 0.320

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.010
DANN	Benign	0.61
PhyloP100		-6.7
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: rs496888; hg19: chr1-12232806; COSMIC: COSV66163775;