rs12029576

Variant summary

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

The NM_003238.6(TGFB2):​c.347-19036C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,026 control chromosomes in the GnomAD database, including 26,138 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 0.55 ( 26138 hom., cov: 32)

Consequence

TGFB2
NM_003238.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.722
Variant links:
Genes affected
TGFB2 (HGNC:11768): (transforming growth factor beta 2) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers. A chromosomal translocation that includes this gene is associated with Peters' anomaly, a congenital defect of the anterior chamber of the eye. Mutations in this gene may be associated with Loeys-Dietz syndrome. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TGFB2NM_003238.6 linkuse as main transcriptc.347-19036C>A intron_variant ENST00000366930.9
TGFB2NM_001135599.4 linkuse as main transcriptc.431-19036C>A intron_variant
TGFB2NR_138148.2 linkuse as main transcriptn.1713-19036C>A intron_variant, non_coding_transcript_variant
TGFB2NR_138149.2 linkuse as main transcriptn.1797-19036C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGFB2ENST00000366930.9 linkuse as main transcriptc.347-19036C>A intron_variant 1 NM_003238.6 P1P61812-1
TGFB2ENST00000366929.4 linkuse as main transcriptc.431-19036C>A intron_variant 1 P61812-2
TGFB2ENST00000488793.1 linkuse as main transcriptn.11-19036C>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.545
AC:
82863
AN:
151908
Hom.:
26138
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.210
Gnomad AMI
AF:
0.775
Gnomad AMR
AF:
0.636
Gnomad ASJ
AF:
0.653
Gnomad EAS
AF:
0.493
Gnomad SAS
AF:
0.551
Gnomad FIN
AF:
0.702
Gnomad MID
AF:
0.583
Gnomad NFE
AF:
0.699
Gnomad OTH
AF:
0.576
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.545
AC:
82884
AN:
152026
Hom.:
26138
Cov.:
32
AF XY:
0.548
AC XY:
40733
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.209
Gnomad4 AMR
AF:
0.636
Gnomad4 ASJ
AF:
0.653
Gnomad4 EAS
AF:
0.494
Gnomad4 SAS
AF:
0.552
Gnomad4 FIN
AF:
0.702
Gnomad4 NFE
AF:
0.699
Gnomad4 OTH
AF:
0.576
Alfa
AF:
0.652
Hom.:
16591
Bravo
AF:
0.524
Asia WGS
AF:
0.532
AC:
1849
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
5.3
DANN
Benign
0.79

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: rs12029576; hg19: chr1-218559475; API