Genetic Variant TGFBR1:c.1131-402T>G (chr9-99146083-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 NM_004612.4(TGFBR1):c.1131-402T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 289,978 control chromosomes in the GnomAD database, including 10,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.26 ( 5219 hom., cov: 31)

Exomes 𝑓: 0.26 ( 5073 hom. )

Consequence

TGFBR1
NM_004612.4 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.876

Publications

53 publications found

Variant links:

Genes affected

TGFBR1 (HGNC:11772): (transforming growth factor beta receptor 1) The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

TGFBR1 links:

RNA5SP290 (HGNC:43190): (RNA, 5S ribosomal pseudogene 290)

RNA5SP290 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR1	NM_004612.4 link	c.1131-402T>G		intron_variant	Intron 6 of 8	ENST00000374994.9	NP_004603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR1	ENST00000374994.9 link	c.1131-402T>G		intron_variant	Intron 6 of 8	1	NM_004612.4	ENSP00000364133.4

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39060

AN:

151892

Hom.:

5210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.257

GnomAD4 exome

AF:

0.262

AC:

36190

AN:

137966

Hom.:

5073

AF XY:

0.266

AC XY:

20183

AN XY:

75814

show subpopulations

African (AFR)

AF:

0.232

AC:

687

AN:

2966

American (AMR)

AF:

0.254

AC:

1171

AN:

4612

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

737

AN:

3120

East Asian (EAS)

AF:

0.447

AC:

2320

AN:

5188

South Asian (SAS)

AF:

0.307

AC:

7726

AN:

25190

European-Finnish (FIN)

AF:

0.196

AC:

1224

AN:

6234

Middle Eastern (MID)

AF:

0.173

AC:

AN:

498

European-Non Finnish (NFE)

AF:

0.247

AC:

20583

AN:

83454

Other (OTH)

AF:

0.247

AC:

1656

AN:

6704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1243

2485

3728

4970

6213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<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:

0.257

AC:

39117

AN:

152012

Hom.:

5219

Cov.:

AF XY:

0.256

AC XY:

18995

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.247

AC:

10223

AN:

41446

American (AMR)

AF:

0.273

AC:

4164

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

821

AN:

3470

East Asian (EAS)

AF:

0.432

AC:

2225

AN:

5154

South Asian (SAS)

AF:

0.314

AC:

1511

AN:

4808

European-Finnish (FIN)

AF:

0.200

AC:

2120

AN:

10580

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17263

AN:

67966

Other (OTH)

AF:

0.260

AC:

548

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1477

2954

4430

5907

7384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.254

Hom.:

15606

Bravo

AF:

0.259

Asia WGS

AF:

0.372

AC:

1292

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

Department of Ophthalmology and Visual Sciences Kyoto University

Significance:not provided

Review Status:no classification provided

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.68

(source)

DANN

Benign

0.51

PhyloP100

-0.88

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over