rs472093

Variant names:

• chr1-12191134-T-A
• rs472093
• NM_001066.3:c.307+49T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-12191134-T-A
• chr1-12191134-T-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.307+49T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,591,908 control chromosomes in the GnomAD database, including 25,437 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 0.15 (1806 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23631 hom.)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 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.307+49T>A		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.307+49T>A		intron	N/A	ENSP00000365435.3	P20333-1
	TNFRSF1B	ENST00000536782.2	TSL:1	c.307+49T>A		intron	N/A	ENSP00000440425.1	B5A977
	TNFRSF1B	ENST00000492361.1	TSL:1	n.296+49T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22124 AN: 152082 Hom.: 1801 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.167 AC: 40276 AN: 241524 AF XY: 0.174

Gnomad AFR exome AF: 0.0830

Gnomad AMR exome AF: 0.0982

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.178 AC: 255907 AN: 1439708 Hom.: 23631 Cov.: 31 AF XY: 0.180 AC XY: 128532 AN XY: 713382

African (AFR) AF: 0.0832 AC: 2738 AN: 32922

American (AMR) AF: 0.0999 AC: 4285 AN: 42914

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5748 AN: 25348

East Asian (EAS) AF: 0.124 AC: 4885 AN: 39242

South Asian (SAS) AF: 0.228 AC: 19411 AN: 85018

European-Finnish (FIN) AF: 0.157 AC: 8098 AN: 51672

Middle Eastern (MID) AF: 0.236 AC: 1261 AN: 5332

European-Non Finnish (NFE) AF: 0.181 AC: 199098 AN: 1097992

Other (OTH) AF: 0.175 AC: 10383 AN: 59268

GnomAD4 genome AF: 0.146 AC: 22156 AN: 152200 Hom.: 1806 Cov.: 32 AF XY: 0.145 AC XY: 10821 AN XY: 74420

African (AFR) AF: 0.0817 AC: 3393 AN: 41540

American (AMR) AF: 0.113 AC: 1723 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3468

East Asian (EAS) AF: 0.133 AC: 687 AN: 5178

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1615 AN: 10588

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12381 AN: 67990

Other (OTH) AF: 0.157 AC: 331 AN: 2110

Alfa AF: 0.169 Hom.: 498

Bravo AF: 0.139

Asia WGS AF: 0.157 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.031
DANN	Benign	0.53
PhyloP100		-1.5
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: rs472093; hg19: chr1-12251191; COSMIC: COSV66164361; COSMIC: COSV66164361;