9-99146083-T-G

Position:

• chr9-99146083-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.876

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 -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/exons	MANE	Protein	UniProt
TGFBR1	NM_004612.4	c.1131-402T>G		intron_variant		ENST00000374994.9	NP_004603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR1	ENST00000374994.9	c.1131-402T>G		intron_variant		1	NM_004612.4	ENSP00000364133	P4

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39060 AN: 151892 Hom.: 5210 Cov.: 31

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

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.254

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.257 AC: 39117 AN: 152012 Hom.: 5219 Cov.: 31 AF XY: 0.256 AC XY: 18995 AN XY: 74294

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.260

Alfa AF: 0.248 Hom.: 5925

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

Submissions by phenotype

not provided Other:1

not provided, no classification provided

not provided

Department of Ophthalmology and Visual Sciences Kyoto University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.51

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: rs334353; hg19: chr9-101908365;