9-99112032-C-T

Position:

• chr9-99112032-C-T

Variant summary

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

The NM_004612.4(TGFBR1):​c.97+6730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,980 control chromosomes in the GnomAD database, including 3,343 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 0.20 (3343 hom., cov: 30)
• Consequence: TGFBR1 NM_004612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR1	NM_004612.4	c.97+6730C>T		intron_variant		ENST00000374994.9	NP_004603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR1	ENST00000374994.9	c.97+6730C>T		intron_variant		1	NM_004612.4	ENSP00000364133.4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30731 AN: 151862 Hom.: 3336 Cov.: 30

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.202 AC: 30774 AN: 151980 Hom.: 3343 Cov.: 30 AF XY: 0.201 AC XY: 14901 AN XY: 74256

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.205

Alfa AF: 0.109 Hom.: 176

Bravo AF: 0.206

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.2
DANN	Benign	0.29
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: rs10819638; hg19: chr9-101874314;