1-12172749-T-C

Variant names:

• chr1-12172749-T-C
• rs496888
• NM_001066.3:c.78+5580T>C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3	c.78+5580T>C		intron_variant	Intron 1 of 9	ENST00000376259.7	NP_001057.1
TNFRSF1B	XM_011542060.3	c.78+5580T>C		intron_variant	Intron 1 of 10		XP_011540362.1
TNFRSF1B	XM_047429422.1	c.78+5580T>C		intron_variant	Intron 1 of 10		XP_047285378.1
TNFRSF1B	XM_011542063.3	c.78+5580T>C		intron_variant	Intron 1 of 9		XP_011540365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.78+5580T>C		intron_variant	Intron 1 of 9	1	NM_001066.3	ENSP00000365435.3
TNFRSF1B	ENST00000536782.2	c.78+5580T>C		intron_variant	Intron 1 of 4	1		ENSP00000440425.1
TNFRSF1B	ENST00000492361.1	n.167+5580T>C		intron_variant	Intron 1 of 8	1

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

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.310

Alfa AF: 0.303 Hom.: 10031

Bravo AF: 0.320

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.010
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs496888; hg19: chr1-12232806; COSMIC: COSV66163775;