dbSNP rs5030792: TNFRSF1B:n.1568T>G (chr1-12207213-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000492361.1(TNFRSF1B):n.1568T>G variant causes a non coding transcript exon 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
ENST00000492361.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

12 publications found

Variant links:

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]

TNFRSF1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3 link	c.*193T>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000376259.7	NP_001057.1	P20333-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000492361.1 link	n.1568T>G		non_coding_transcript_exon_variant	Exon 9 of 9	1
TNFRSF1B	ENST00000376259.7 link	c.*193T>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_001066.3	ENSP00000365435.3		P20333-1

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

4969

AN:

152126

Hom.:

126

Cov.:

show subpopulations

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.:

AF XY:

0.0445

AC XY:

8319

AN XY:

186806

show subpopulations

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:

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:

AN:

1712

European-Non Finnish (NFE)

AF:

0.0541

AC:

13179

AN:

243526

Other (OTH)

AF:

0.0445

AC:

962

AN:

21618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

761

1523

2284

3046

3807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0327

AC:

4972

AN:

152244

Hom.:

126

Cov.:

AF XY:

0.0306

AC XY:

2281

AN XY:

74438

show subpopulations

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:

AN:

5174

South Asian (SAS)

AF:

0.0127

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0224

AC:

238

AN:

10610

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0504

AC:

3427

AN:

68010

Other (OTH)

AF:

0.0427

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

257

515

772

1030

1287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0410

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.7

(source)

DANN

Benign

0.66

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over