Variant chr9-99138128-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004612.4(TGFBR1):c.805+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,549,336 control chromosomes in the GnomAD database, including 5,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 591 hom., cov: 32)

Exomes 𝑓: 0.026 ( 4463 hom. )

Consequence

TGFBR1
NM_004612.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.83

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-99138128-A-G is Benign according to our data. Variant chr9-99138128-A-G is described in ClinVar as [Benign]. Clinvar id is 259453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR1	NM_004612.4 linkuse as main transcript	c.805+39A>G		intron_variant		ENST00000374994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR1	ENST00000374994.9 linkuse as main transcript	c.805+39A>G		intron_variant		1	NM_004612.4	P4	P36897-1

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4869

AN:

152174

Hom.:

594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0999

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00334

Gnomad OTH

AF:

0.0297

GnomAD3 exomes

AF:

0.0665

AC:

16409

AN:

246870

Hom.:

2208

AF XY:

0.0635

AC XY:

8497

AN XY:

133776

show subpopulations

Gnomad AFR exome

AF:

0.00570

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.429

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.00310

Gnomad OTH exome

AF:

0.0390

GnomAD4 exome

AF:

0.0256

AC:

35779

AN:

1397042

Hom.:

4463

Cov.:

AF XY:

0.0273

AC XY:

19054

AN XY:

698608

show subpopulations

Gnomad4 AFR exome

AF:

0.00524

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.00219

Gnomad4 OTH exome

AF:

0.0356

GnomAD4 genome

AF:

0.0320

AC:

4869

AN:

152294

Hom.:

591

Cov.:

AF XY:

0.0371

AC XY:

2762

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00563

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.00334

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0167

Hom.:

Bravo

AF:

0.0375

Asia WGS

AF:

0.250

AC:

869

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 10, 2018	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Multiple self-healing squamous epithelioma

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.9

DANN

Benign

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over