rs876688

chr3-30684284-G-A

Variant summary

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

The NM_003242.6(TGFBR2):c.1397-4100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,778 control chromosomes in the GnomAD database, including 10,912 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 0.37 (10912 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR2	NM_003242.6	c.1397-4100G>A		intron_variant		ENST00000295754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR2	ENST00000295754.10	c.1397-4100G>A		intron_variant		1	NM_003242.6	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56706 AN: 151662 Hom.: 10890 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.374 AC: 56777 AN: 151778 Hom.: 10912 Cov.: 31 AF XY: 0.376 AC XY: 27879 AN XY: 74144

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.327

Alfa AF: 0.353 Hom.: 12521

Bravo AF: 0.380

Asia WGS AF: 0.236 AC: 818 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.34
Dann	Benign	0.16

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: rs876688; hg19: chr3-30725776;