rs747857

chr19-41331842-G-Achr19-41331842-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000660.7(TGFB1):c.1014+286C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 150,954 control chromosomes in the GnomAD database, including 830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.063 (830 hom., cov: 28)
• Consequence: TGFB1 NM_000660.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.370

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 19-41331842-G-A is Benign according to our data. Variant chr19-41331842-G-A is described in ClinVar as [Benign]. Clinvar id is 1230600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFB1	NM_000660.7	c.1014+286C>T		intron_variant		ENST00000221930.6
TGFB1	XM_011527242.3	c.1017+286C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFB1	ENST00000221930.6	c.1014+286C>T		intron_variant		1	NM_000660.7	P1
TGFB1	ENST00000600196.2	c.954+198C>T		intron_variant		5
TGFB1	ENST00000677934.1	c.788+286C>T		intron_variant
TGFB1	ENST00000598758.5	n.302+286C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9513 AN: 150834 Hom.: 817 Cov.: 28

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0473

Gnomad ASJ AF: 0.00635

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.00298

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00217

Gnomad OTH AF: 0.0506

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

GnomAD4 genome AF: 0.0633 AC: 9557 AN: 150954 Hom.: 830 Cov.: 28 AF XY: 0.0645 AC XY: 4753 AN XY: 73692

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0472

Gnomad4 ASJ AF: 0.00635

Gnomad4 EAS AF: 0.0682

Gnomad4 SAS AF: 0.0727

Gnomad4 FIN AF: 0.00298

Gnomad4 NFE AF: 0.00217

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0397 Hom.: 67

Bravo AF: 0.0726

Asia WGS AF: 0.0910 AC: 314 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	2.8
Dann	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs747857; hg19: chr19-41837747;