3-30645248-G-A

Position:

• chr3-30645248-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.263+333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,694 control chromosomes in the GnomAD database, including 9,592 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 0.35 (9592 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.263+333G>A		intron_variant		ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.263+333G>A		intron_variant		1	NM_003242.6	ENSP00000295754	P1
TGFBR2	ENST00000359013.4	c.338+333G>A		intron_variant		1		ENSP00000351905
TGFBR2	ENST00000672866.1	n.1859+333G>A		intron_variant, non_coding_transcript_variant
TGFBR2	ENST00000673250.1	n.387+333G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52830 AN: 151576 Hom.: 9600 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.348 AC: 52843 AN: 151694 Hom.: 9592 Cov.: 31 AF XY: 0.351 AC XY: 25980 AN XY: 74094

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.330

Alfa AF: 0.340 Hom.: 5862

Bravo AF: 0.343

Asia WGS AF: 0.501 AC: 1746 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	7.9
DANN	Benign	0.74

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: rs1155708; hg19: chr3-30686740;