dbSNP rs1061624: TNFRSF1B:n.1563A>G (chr1-12207208-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 ENST00000492361.1(TNFRSF1B):n.1563A>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 0.515 in 537,976 control chromosomes in the GnomAD database, including 73,598 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 0.48 ( 18701 hom., cov: 32)

Exomes 𝑓: 0.53 ( 54897 hom. )

Consequence

TNFRSF1B
ENST00000492361.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.727

Publications

102 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:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3 link	c.*188A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000376259.7	NP_001057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000492361.1 link	n.1563A>G		non_coding_transcript_exon_variant	Exon 9 of 9	1
TNFRSF1B	ENST00000376259.7 link	c.*188A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_001066.3	ENSP00000365435.3

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73596

AN:

151978

Hom.:

18690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.504

GnomAD4 exome

AF:

0.528

AC:

203666

AN:

385880

Hom.:

54897

Cov.:

AF XY:

0.526

AC XY:

103461

AN XY:

196520

show subpopulations

African (AFR)

AF:

0.320

AC:

3374

AN:

10528

American (AMR)

AF:

0.562

AC:

6952

AN:

12368

Ashkenazi Jewish (ASJ)

AF:

0.483

AC:

5466

AN:

11306

East Asian (EAS)

AF:

0.501

AC:

13096

AN:

26126

South Asian (SAS)

AF:

0.460

AC:

8399

AN:

18256

European-Finnish (FIN)

AF:

0.647

AC:

16009

AN:

24738

Middle Eastern (MID)

AF:

0.495

AC:

872

AN:

1760

European-Non Finnish (NFE)

AF:

0.534

AC:

137991

AN:

258338

Other (OTH)

AF:

0.512

AC:

11507

AN:

22460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4676

9352

14029

18705

23381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1634

3268

4902

6536

8170

<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:

0.484

AC:

73613

AN:

152096

Hom.:

18701

Cov.:

AF XY:

0.491

AC XY:

36484

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.330

AC:

13693

AN:

41494

American (AMR)

AF:

0.548

AC:

8377

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

1668

AN:

3470

East Asian (EAS)

AF:

0.533

AC:

2745

AN:

5148

South Asian (SAS)

AF:

0.462

AC:

2222

AN:

4812

European-Finnish (FIN)

AF:

0.659

AC:

6990

AN:

10604

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.536

AC:

36403

AN:

67966

Other (OTH)

AF:

0.499

AC:

1053

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1911

3822

5734

7645

9556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.539

Hom.:

19516

Bravo

AF:

0.471

Asia WGS

AF:

0.430

AC:

1496

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.4

(source)

DANN

Benign

0.48

PhyloP100

0.73

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