Variant chr1-218345173-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The ENST00000414452.2(TGFB2-AS1):n.627+2T>G variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,360 control chromosomes in the GnomAD database, including 6,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 6580 hom., cov: 32)

Exomes 𝑓: 0.083 ( 4 hom. )

Consequence

TGFB2-AS1
ENST00000414452.2 splice_donor, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.326

Variant links:

Genes affected

TGFB2-AS1 (HGNC:50628): (TGFB2 antisense RNA 1 (head to head))

TGFB2-AS1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene.

BP6

Variant 1-218345173-A-C is Benign according to our data. Variant chr1-218345173-A-C is described in ClinVar as [Benign]. Clinvar id is 1241729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFB2	NM_003238.6 link	c.-1529A>C		upstream_gene_variant		ENST00000366930.9	NP_003229.1	P61812-1Q59EG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFB2	ENST00000366930.9 link	c.-1529A>C		upstream_gene_variant		1	NM_003238.6	ENSP00000355897.4		P61812-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28029

AN:

152086

Hom.:

6555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0889

Gnomad ASJ

AF:

0.0426

Gnomad EAS

AF:

0.0827

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0381

Gnomad OTH

AF:

0.137

GnomAD4 exome

AF:

0.0833

AC:

AN:

156

Hom.:

Cov.:

AF XY:

0.0789

AC XY:

AN XY:

114

show subpopulations

Gnomad4 AFR exome

AF:

0.750

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0268

Gnomad4 OTH exome

AF:

0.0500

GnomAD4 genome

AF:

0.185

AC:

28106

AN:

152204

Hom.:

6580

Cov.:

AF XY:

0.178

AC XY:

13219

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.553

Gnomad4 AMR

AF:

0.0887

Gnomad4 ASJ

AF:

0.0426

Gnomad4 EAS

AF:

0.0827

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.0222

Gnomad4 NFE

AF:

0.0381

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.107

Hom.:

1259

Bravo

AF:

0.208

Asia WGS

AF:

0.0610

AC:

212

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Benign

0.58

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over