rs10739778

Positions:

• chr9-99113507-A-C
• chr9-99113507-A-G

Variant summary

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

The ENST00000374994.9(TGFBR1):​c.97+8205A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,990 control chromosomes in the GnomAD database, including 9,769 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 0.36 (9769 hom., cov: 32)
• Consequence: TGFBR1 ENST00000374994.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR1	NM_004612.4	c.97+8205A>C		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+8205A>C		intron_variant		1	NM_004612.4	ENSP00000364133	P4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54021 AN: 151872 Hom.: 9748 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.356 AC: 54098 AN: 151990 Hom.: 9769 Cov.: 32 AF XY: 0.354 AC XY: 26336 AN XY: 74296

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.356

Alfa AF: 0.336 Hom.: 11486

Bravo AF: 0.355

Asia WGS AF: 0.416 AC: 1446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.3
DANN	Benign	0.84

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: rs10739778; hg19: chr9-101875789;