rs11466493

chr3-30645290-C-Gchr3-30645290-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003242.6(TGFBR2):c.263+375C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 152,162 control chromosomes in the GnomAD database, including 115 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 0.037 (115 hom., cov: 31)
• Consequence: TGFBR2 NM_003242.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0371 (5651/152162) while in subpopulation NFE AF= 0.0452 (3077/68002). AF 95% confidence interval is 0.0439. There are 115 homozygotes in gnomad4. There are 2648 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 5651 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR2	NM_003242.6	c.263+375C>G		intron_variant		ENST00000295754.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR2	ENST00000295754.10	c.263+375C>G		intron_variant		1	NM_003242.6	P1
TGFBR2	ENST00000359013.4	c.338+375C>G		intron_variant		1
TGFBR2	ENST00000672866.1	n.1859+375C>G		intron_variant, non_coding_transcript_variant
TGFBR2	ENST00000673250.1	n.387+375C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5651 AN: 152044 Hom.: 115 Cov.: 31

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0390

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0446

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

GnomAD4 genome AF: 0.0371 AC: 5651 AN: 152162 Hom.: 115 Cov.: 31 AF XY: 0.0356 AC XY: 2648 AN XY: 74390

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.0390

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.00484

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0347

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0150 Hom.: 11

Bravo AF: 0.0376

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	8.7
Dann	Benign	0.59

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: rs11466493; hg19: chr3-30686782;