rs3773634

Positions:

• chr3-30656444-A-G

Variant summary

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

The ENST00000295754.10(TGFBR2):​c.454+5984A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,120 control chromosomes in the GnomAD database, including 8,696 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 0.33 (8696 hom., cov: 32)
• Consequence: TGFBR2 ENST00000295754.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

Genes affected

TGFBR2 (HGNC:11773): (transforming growth factor beta receptor 2) The protein encoded by this gene is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with TGF-beta receptor type-1, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of genes related to cell proliferation, cell cycle arrest, wound healing, immunosuppression, and tumorigenesis. Mutations in this gene have been associated with Marfan Syndrome, Loeys-Deitz Aortic Aneurysm Syndrome, and the development of various types of tumors. Alternatively spliced transcript variants encoding different isoforms have been characterized. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.454+5984A>G		intron_variant		ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.454+5984A>G		intron_variant		1	NM_003242.6	ENSP00000295754	P1
TGFBR2	ENST00000359013.4	c.529+5984A>G		intron_variant		1		ENSP00000351905
TGFBR2	ENST00000672866.1	n.2050+5984A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49480 AN: 152002 Hom.: 8673 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.326 AC: 49564 AN: 152120 Hom.: 8696 Cov.: 32 AF XY: 0.325 AC XY: 24146 AN XY: 74366

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.313

Alfa AF: 0.309 Hom.: 1369

Bravo AF: 0.319

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3773634; hg19: chr3-30697936;