rs334349

chr9-99152105-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004612.4(TGFBR1):c.*2800G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 206,368 control chromosomes in the GnomAD database, including 9,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6167 hom., cov: 31)
  • Exomes 𝑓: 0.31 (2902 hom.)
• Consequence: TGFBR1 NM_004612.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-99152105-G-A is Benign according to our data. Variant chr9-99152105-G-A is described in ClinVar as [Benign]. Clinvar id is 364155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR1	NM_004612.4	c.*2800G>A		3_prime_UTR_variant	9/9	ENST00000374994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR1	ENST00000374994.9	c.*2800G>A		3_prime_UTR_variant	9/9	1	NM_004612.4	P4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42447 AN: 151784 Hom.: 6148 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.306 AC: 16682 AN: 54466 Hom.: 2902 Cov.: 0 AF XY: 0.304 AC XY: 7708 AN XY: 25324

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.539

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.280 AC: 42517 AN: 151902 Hom.: 6167 Cov.: 31 AF XY: 0.278 AC XY: 20642 AN XY: 74232

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.279

Alfa AF: 0.268 Hom.: 3796

Bravo AF: 0.283

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Loeys-Dietz syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Loeys-Dietz syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.032
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs334349; hg19: chr9-101914387;