dbSNP rs2026811: TGFBR1:c.97+11679C>A (chr9-99116981-C-A) – 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.97+11679C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,008 control chromosomes in the GnomAD database, including 4,886 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 0.25 ( 4886 hom., cov: 32)

Consequence

TGFBR1
NM_004612.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00900

Publications

10 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 Gene-Disease associations (from GenCC):

familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Loeys-Dietz syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Loeys-Dietz syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Genomics England PanelApp, G2P
multiple self-healing squamous epithelioma
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

TGFBR1 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR1	NM_004612.4 link	c.97+11679C>A		intron_variant	Intron 1 of 8	ENST00000374994.9	NP_004603.1	P36897-1Q5T7S2B4DXN7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR1	ENST00000374994.9 link	c.97+11679C>A		intron_variant	Intron 1 of 8	1	NM_004612.4	ENSP00000364133.4		P36897-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37322

AN:

151890

Hom.:

4870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.246

AC:

37382

AN:

152008

Hom.:

4886

Cov.:

AF XY:

0.243

AC XY:

18064

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.298

AC:

12345

AN:

41430

American (AMR)

AF:

0.253

AC:

3866

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

717

AN:

3470

East Asian (EAS)

AF:

0.468

AC:

2419

AN:

5174

South Asian (SAS)

AF:

0.231

AC:

1115

AN:

4820

European-Finnish (FIN)

AF:

0.154

AC:

1630

AN:

10566

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14585

AN:

67950

Other (OTH)

AF:

0.237

AC:

502

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1421

2842

4262

5683

7104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.219

Hom.:

2016

Bravo

AF:

0.253

Asia WGS

AF:

0.361

AC:

1257

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.84

(source)

DANN

Benign

0.38

PhyloP100

-0.0090

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over