3-30632762-C-T

Position:

• chr3-30632762-C-T

Variant summary

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

The NM_001407133.1(TGFBR2):​c.-96C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 152,164 control chromosomes in the GnomAD database, including 472 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 0.060 (472 hom., cov: 32)
• Consequence: TGFBR2 NM_001407133.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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]

TGFBR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR2	NM_003242.6	c.95-11985C>T		intron_variant		ENST00000295754.10	NP_003233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR2	ENST00000295754.10	c.95-11985C>T		intron_variant		1	NM_003242.6	ENSP00000295754.5
TGFBR2	ENST00000359013.4	c.169+9489C>T		intron_variant		1		ENSP00000351905.4
TGFBR2	ENST00000672866.1	n.1606C>T		non_coding_transcript_exon_variant	1/7
TGFBR2	ENST00000673250.1	n.218+9489C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0602 AC: 9151 AN: 152046 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0575

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

GnomAD4 genome AF: 0.0601 AC: 9143 AN: 152164 Hom.: 472 Cov.: 32 AF XY: 0.0654 AC XY: 4864 AN XY: 74408

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0441 Hom.: 233

Bravo AF: 0.0583

Asia WGS AF: 0.222 AC: 770 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.80

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: rs12490899; hg19: chr3-30674254;