rs10733710

chr9-99145142-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004612.4(TGFBR1):c.1130+254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,104 control chromosomes in the GnomAD database, including 3,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3540 hom., cov: 32)
• Consequence: TGFBR1 NM_004612.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.431

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-99145142-G-A is Benign according to our data. Variant chr9-99145142-G-A is described in ClinVar as [Benign]. Clinvar id is 683995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR1	NM_004612.4	c.1130+254G>A		intron_variant		ENST00000374994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR1	ENST00000374994.9	c.1130+254G>A		intron_variant		1	NM_004612.4	P4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31906 AN: 151986 Hom.: 3540 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.210 AC: 31912 AN: 152104 Hom.: 3540 Cov.: 32 AF XY: 0.215 AC XY: 15997 AN XY: 74374

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.219

Alfa AF: 0.220 Hom.: 5134

Bravo AF: 0.210

Asia WGS AF: 0.264 AC: 919 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.29
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10733710; hg19: chr9-101907424;