rs2026811

Positions:

• chr9-99116981-C-A

Variant summary

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

The NM_004612.4(TGFBR1):​c.97+11679C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,008 control chromosomes in the GnomAD database, including 4,886 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 0.25 (4886 hom., cov: 32)
• Consequence: TGFBR1 NM_004612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.9).
• 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	UniProt
TGFBR1	NM_004612.4	c.97+11679C>A		intron_variant		ENST00000374994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR1	ENST00000374994.9	c.97+11679C>A		intron_variant		1	NM_004612.4	P4

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37322 AN: 151890 Hom.: 4870 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.246 AC: 37382 AN: 152008 Hom.: 4886 Cov.: 32 AF XY: 0.243 AC XY: 18064 AN XY: 74296

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.237

Alfa AF: 0.219 Hom.: 1799

Bravo AF: 0.253

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.38

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: rs2026811; hg19: chr9-101879263;