rs1418553

Positions:

• chr1-218436912-C-T

Variant summary

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

The NM_003238.6(TGFB2):​c.933-431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,024 control chromosomes in the GnomAD database, including 11,638 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 0.38 (11638 hom., cov: 32)
• Consequence: TGFB2 NM_003238.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769

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]

TGFB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFB2	NM_003238.6	c.933-431C>T		intron_variant		ENST00000366930.9	NP_003229.1
TGFB2	NM_001135599.4	c.1017-431C>T		intron_variant			NP_001129071.1
TGFB2	NR_138148.2	n.2184-431C>T		intron_variant
TGFB2	NR_138149.2	n.2268-431C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB2	ENST00000366930.9	c.933-431C>T		intron_variant		1	NM_003238.6	ENSP00000355897.4
TGFB2	ENST00000366929.4	c.1017-431C>T		intron_variant		1		ENSP00000355896.4
TGFB2	ENST00000479322.1	n.417-431C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57036 AN: 151906 Hom.: 11617 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.376 AC: 57102 AN: 152024 Hom.: 11638 Cov.: 32 AF XY: 0.381 AC XY: 28301 AN XY: 74286

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.370

Alfa AF: 0.348 Hom.: 1728

Bravo AF: 0.394

Asia WGS AF: 0.493 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
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: rs1418553; hg19: chr1-218610254;