rs12980942

chr19-41326326-G-A

Variant summary

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

The ENST00000598758.5(TGFB1):n.302+5802C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,214 control chromosomes in the GnomAD database, including 1,549 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 0.13 (1549 hom., cov: 32)
• Consequence: TGFB1 ENST00000598758.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

Genes affected

TGFB1 (HGNC:11766): (transforming growth factor beta 1) 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 TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [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 (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFB1	ENST00000598758.5	n.302+5802C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19655 AN: 152096 Hom.: 1553 Cov.: 32

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.0956

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.129 AC: 19643 AN: 152214 Hom.: 1549 Cov.: 32 AF XY: 0.127 AC XY: 9449 AN XY: 74406

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.136

Alfa AF: 0.148 Hom.: 387

Bravo AF: 0.128

Asia WGS AF: 0.190 AC: 661 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	3.8
Dann	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12980942; hg19: chr19-41832231;