rs1346907

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003242.6(TGFBR2):​c.1397-6406A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,150 control chromosomes in the GnomAD database, including 28,830 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 0.61 ( 28830 hom., cov: 33)

Consequence

TGFBR2
NM_003242.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TGFBR2NM_003242.6 linkc.1397-6406A>G intron_variant ENST00000295754.10 NP_003233.4 P37173-1A3QNQ0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TGFBR2ENST00000295754.10 linkc.1397-6406A>G intron_variant 1 NM_003242.6 ENSP00000295754.5 P37173-1

Frequencies

GnomAD3 genomes
AF:
0.608
AC:
92365
AN:
152032
Hom.:
28775
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.747
Gnomad AMI
AF:
0.474
Gnomad AMR
AF:
0.598
Gnomad ASJ
AF:
0.452
Gnomad EAS
AF:
0.661
Gnomad SAS
AF:
0.544
Gnomad FIN
AF:
0.624
Gnomad MID
AF:
0.456
Gnomad NFE
AF:
0.535
Gnomad OTH
AF:
0.542
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.608
AC:
92464
AN:
152150
Hom.:
28830
Cov.:
33
AF XY:
0.611
AC XY:
45439
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.748
Gnomad4 AMR
AF:
0.598
Gnomad4 ASJ
AF:
0.452
Gnomad4 EAS
AF:
0.661
Gnomad4 SAS
AF:
0.542
Gnomad4 FIN
AF:
0.624
Gnomad4 NFE
AF:
0.535
Gnomad4 OTH
AF:
0.539
Alfa
AF:
0.540
Hom.:
45922
Bravo
AF:
0.613
Asia WGS
AF:
0.602
AC:
2092
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.083
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1346907; hg19: chr3-30723470; API