1-218386133-C-A

Position:

• chr1-218386133-C-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722

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]

ACMG classification

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	Protein	UniProt
TGFB2	NM_003238.6	c.347-19036C>A		intron_variant		ENST00000366930.9	NP_003229.1
TGFB2	NM_001135599.4	c.431-19036C>A		intron_variant			NP_001129071.1
TGFB2	NR_138148.2	n.1713-19036C>A		intron_variant, non_coding_transcript_variant
TGFB2	NR_138149.2	n.1797-19036C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB2	ENST00000366930.9	c.347-19036C>A		intron_variant		1	NM_003238.6	ENSP00000355897	P1
TGFB2	ENST00000366929.4	c.431-19036C>A		intron_variant		1		ENSP00000355896
TGFB2	ENST00000488793.1	n.11-19036C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82863 AN: 151908 Hom.: 26138 Cov.: 32

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

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

Other links and lift over

dbSNP: rs12029576; hg19: chr1-218559475;