chr19-41345604-C-A

Position:

• chr19-41345604-C-A

Variant summary

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

The NM_000660.7(TGFB1):​c.517-740G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,770 control chromosomes in the GnomAD database, including 19,658 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 0.50 (19658 hom., cov: 33)
• Consequence: TGFB1 NM_000660.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFB1	NM_000660.7	c.517-740G>T		intron_variant		ENST00000221930.6	NP_000651.3
TGFB1	XM_011527242.3	c.517-740G>T		intron_variant			XP_011525544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB1	ENST00000221930.6	c.517-740G>T		intron_variant		1	NM_000660.7	ENSP00000221930	P1
TGFB1	ENST00000597453.1	n.48-740G>T		intron_variant, non_coding_transcript_variant		1
TGFB1	ENST00000600196.2	c.517-740G>T		intron_variant		5		ENSP00000504008
TGFB1	ENST00000677934.1	c.517-740G>T		intron_variant				ENSP00000504769

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76488 AN: 151648 Hom.: 19658 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.504 AC: 76518 AN: 151770 Hom.: 19658 Cov.: 33 AF XY: 0.505 AC XY: 37419 AN XY: 74152

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.475

Alfa AF: 0.481 Hom.: 36100

Bravo AF: 0.491

Asia WGS AF: 0.423 AC: 1467 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	7.2
DANN	Benign	0.63

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: rs4803455; hg19: chr19-41851509;