3-30627192-A-G

Position:

• chr3-30627192-A-G

Variant summary

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

The NM_003242.6(TGFBR2):​c.95-17555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,966 control chromosomes in the GnomAD database, including 17,232 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 0.47 (17232 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.95-17555A>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.95-17555A>G		intron_variant		1	NM_003242.6	ENSP00000295754	P1
TGFBR2	ENST00000359013.4	c.169+3919A>G		intron_variant		1		ENSP00000351905
TGFBR2	ENST00000673250.1	n.218+3919A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72128 AN: 151850 Hom.: 17228 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.475 AC: 72176 AN: 151966 Hom.: 17232 Cov.: 31 AF XY: 0.474 AC XY: 35223 AN XY: 74266

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.482

Alfa AF: 0.472 Hom.: 34740

Bravo AF: 0.481

Asia WGS AF: 0.369 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.52

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: rs4522809; hg19: chr3-30668684;