dbSNP rs5746051: TNFRSF1B:c.901-52A>G (chr1-12201915-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0950

Publications

21 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=-0.91).

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 rank	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3 link	c.901-52A>G		intron_variant	Intron 8 of 9	ENST00000376259.7	NP_001057.1	P20333-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7 link	c.901-52A>G		intron_variant	Intron 8 of 9	1	NM_001066.3	ENSP00000365435.3		P20333-1
TNFRSF1B	ENST00000492361.1 link	n.890-52A>G		intron_variant	Intron 7 of 8	1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21241

AN:

152072

Hom.:

1753

Cov.:

show subpopulations

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.:

AF XY:

0.183

AC XY:

122646

AN XY:

671460

show subpopulations

African (AFR)

AF:

0.0539

AC:

1684

AN:

31238

American (AMR)

AF:

0.0949

AC:

3285

AN:

34608

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

4208

AN:

23994

East Asian (EAS)

AF:

0.146

AC:

5199

AN:

35696

South Asian (SAS)

AF:

0.227

AC:

17586

AN:

77640

European-Finnish (FIN)

AF:

0.147

AC:

7101

AN:

48258

Middle Eastern (MID)

AF:

0.209

AC:

1100

AN:

5272

European-Non Finnish (NFE)

AF:

0.187

AC:

197765

AN:

1059428

Other (OTH)

AF:

0.177

AC:

9995

AN:

56566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

11348

22696

34045

45393

56741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7234

14468

21702

28936

36170

<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:

0.140

AC:

21261

AN:

152192

Hom.:

1756

Cov.:

AF XY:

0.139

AC XY:

10375

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0572

AC:

2376

AN:

41550

American (AMR)

AF:

0.111

AC:

1694

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

605

AN:

3470

East Asian (EAS)

AF:

0.165

AC:

856

AN:

5182

South Asian (SAS)

AF:

0.223

AC:

1077

AN:

4822

European-Finnish (FIN)

AF:

0.151

AC:

1606

AN:

10608

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12564

AN:

67962

Other (OTH)

AF:

0.154

AC:

326

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

922

1845

2767

3690

4612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.158

Hom.:

1516

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

(source)

DANN

Benign

0.28

PhyloP100

-0.095

Mutation Taster

=100/0

polymorphism (auto)

(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

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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