Genetic Variant TBL2:c.599-54G>A (chr7-73573024-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_012453.4(TBL2):c.599-54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,609,452 control chromosomes in the GnomAD database, including 58,561 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 0.27 ( 5977 hom., cov: 32)

Exomes 𝑓: 0.26 ( 52584 hom. )

Consequence

TBL2
NM_012453.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

59 publications found

Variant links:

Genes affected

TBL2 (HGNC:11586): (transducin beta like 2) This gene encodes a member of the beta-transducin protein family. Most proteins of the beta-transducin family are involved in regulatory functions. This protein is possibly involved in some intracellular signaling pathway. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23. [provided by RefSeq, Jul 2008]

TBL2 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012453.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBL2	NM_012453.4	MANE Select	c.599-54G>A	intron	N/A	NP_036585.1	Q9Y4P3
TBL2	NM_001362660.2		c.500-54G>A	intron	N/A	NP_001349589.1
TBL2	NM_001362661.2		c.104-54G>A	intron	N/A	NP_001349590.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBL2	ENST00000305632.11	TSL:1 MANE Select	c.599-54G>A	intron	N/A	ENSP00000307260.4	Q9Y4P3
TBL2	ENST00000450285.5	TSL:1	n.*45-54G>A	intron	N/A	ENSP00000409820.1	F8WDI9
TBL2	ENST00000857340.1		c.599-54G>A	intron	N/A	ENSP00000527398.1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41198

AN:

151948

Hom.:

5952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.0990

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.245

GnomAD4 exome

AF:

0.264

AC:

384450

AN:

1457386

Hom.:

52584

Cov.:

AF XY:

0.261

AC XY:

189435

AN XY:

724758

show subpopulations

African (AFR)

AF:

0.342

AC:

11451

AN:

33434

American (AMR)

AF:

0.150

AC:

6666

AN:

44386

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

6168

AN:

25758

East Asian (EAS)

AF:

0.0959

AC:

3804

AN:

39662

South Asian (SAS)

AF:

0.173

AC:

14788

AN:

85702

European-Finnish (FIN)

AF:

0.229

AC:

12161

AN:

53134

Middle Eastern (MID)

AF:

0.290

AC:

1655

AN:

5704

European-Non Finnish (NFE)

AF:

0.282

AC:

312384

AN:

1109402

Other (OTH)

AF:

0.255

AC:

15373

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

15504

31008

46511

62015

77519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10276

20552

30828

41104

51380

<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:

0.271

AC:

41271

AN:

152066

Hom.:

5977

Cov.:

AF XY:

0.266

AC XY:

19768

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.341

AC:

14145

AN:

41456

American (AMR)

AF:

0.204

AC:

3121

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

848

AN:

3472

East Asian (EAS)

AF:

0.0994

AC:

514

AN:

5172

South Asian (SAS)

AF:

0.171

AC:

825

AN:

4820

European-Finnish (FIN)

AF:

0.213

AC:

2256

AN:

10596

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18803

AN:

67956

Other (OTH)

AF:

0.247

AC:

521

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1517

3034

4551

6068

7585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.270

Hom.:

17210

Bravo

AF:

0.274

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.59

(source)

DANN

Benign

0.65

PhyloP100

-1.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over