rs5030792

Variant names:

• chr1-12207213-T-G
• rs5030792
• NM_001066.3:c.*193T>G

Variant summary

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

The NM_001066.3(TNFRSF1B):​c.*193T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 518,788 control chromosomes in the GnomAD database, including 548 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 0.033 (126 hom., cov: 33)
  • Exomes 𝑓: 0.045 (422 hom.)
• Consequence: TNFRSF1B NM_001066.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 12 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=-0.79).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0533 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.*193T>G		3_prime_UTR	Exon 10 of 10	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.*193T>G		3_prime_UTR	Exon 10 of 10	ENSP00000365435.3	P20333-1
	TNFRSF1B	ENST00000492361.1	TSL:1	n.1568T>G		non_coding_transcript_exon	Exon 9 of 9
	TNFRSF1B	ENST00000941756.1		c.*193T>G		3_prime_UTR	Exon 10 of 10	ENSP00000611815.1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4969 AN: 152126 Hom.: 126 Cov.: 33

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0432

GnomAD4 exome AF: 0.0446 AC: 16348 AN: 366544 Hom.: 422 Cov.: 5 AF XY: 0.0445 AC XY: 8319 AN XY: 186806

African (AFR) AF: 0.00978 AC: 100 AN: 10228

American (AMR) AF: 0.0325 AC: 385 AN: 11834

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 837 AN: 11082

East Asian (EAS) AF: 0.0000388 AC: 1 AN: 25768

South Asian (SAS) AF: 0.0163 AC: 269 AN: 16522

European-Finnish (FIN) AF: 0.0214 AC: 519 AN: 24254

Middle Eastern (MID) AF: 0.0561 AC: 96 AN: 1712

European-Non Finnish (NFE) AF: 0.0541 AC: 13179 AN: 243526

Other (OTH) AF: 0.0445 AC: 962 AN: 21618

GnomAD4 genome AF: 0.0327 AC: 4972 AN: 152244 Hom.: 126 Cov.: 33 AF XY: 0.0306 AC XY: 2281 AN XY: 74438

African (AFR) AF: 0.00878 AC: 365 AN: 41552

American (AMR) AF: 0.0334 AC: 511 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4818

European-Finnish (FIN) AF: 0.0224 AC: 238 AN: 10610

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0504 AC: 3427 AN: 68010

Other (OTH) AF: 0.0427 AC: 90 AN: 2106

Alfa AF: 0.0410 Hom.: 18

Bravo AF: 0.0343

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5030792;

hg19: chr1-12267270;