chr1-12201915-A-G

Position:

• chr1-12201915-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF1B	NM_001066.3	c.901-52A>G		intron_variant		ENST00000376259.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.901-52A>G		intron_variant		1	NM_001066.3	P1
TNFRSF1B	ENST00000492361.1	n.890-52A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.0539

Gnomad4 AMR exome AF: 0.0949

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.177

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

Gnomad4 AFR AF: 0.0572

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.154

Alfa AF: 0.173 Hom.: 1109

Bravo AF: 0.132

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.28

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: rs5746051; hg19: chr1-12261972; COSMIC: COSV66163968;