Variant chr14-75963212-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000556285.1(TGFB3):c.*100G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,249,846 control chromosomes in the GnomAD database, including 346,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38508 hom., cov: 30)

Exomes 𝑓: 0.75 ( 307500 hom. )

Consequence

TGFB3
ENST00000556285.1 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.260

Variant links:

Genes affected

TGFB3 (HGNC:11769): (transforming growth factor beta 3) 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. This protein is involved in embryogenesis and cell differentiation, and may play a role in wound healing. Mutations in this gene are a cause of aortic aneurysms and dissections, as well as familial arrhythmogenic right ventricular dysplasia 1. [provided by RefSeq, Aug 2016]

TGFB3 links:

IFT43 (HGNC:29669): (intraflagellar transport 43) This gene encodes a subunit of the intraflagellar transport complex A (IFT-A). IFT-A is a multiprotein complex that plays an important role in cilia assembly and maintenance by mediating retrograde ciliary transport. Mutations in this gene are a cause of cranioectodermal dysplasia-3 (CED3), also known as Sensenbrenner syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

IFT43 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 14-75963212-C-T is Benign according to our data. Variant chr14-75963212-C-T is described in ClinVar as [Benign]. Clinvar id is 1238112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
TGFB3	NM_003239.5 linkuse as main transcript	c.926+104G>A	intron_variant		ENST00000238682.8	NP_003230.1
TGFB3	NM_001329938.2 linkuse as main transcript	c.*100G>A	3_prime_UTR_variant	5/5		NP_001316867.1
TGFB3	NM_001329939.2 linkuse as main transcript	c.926+104G>A	intron_variant			NP_001316868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB3	ENST00000238682.8 linkuse as main transcript	c.926+104G>A		intron_variant		1	NM_003239.5	ENSP00000238682	P1	P10600-1

Frequencies

GnomAD3 genomes

AF:

0.707

AC:

107317

AN:

151872

Hom.:

38496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.711

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.790

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.764

Gnomad OTH

AF:

0.711

GnomAD4 exome

AF:

0.745

AC:

818096

AN:

1097856

Hom.:

307500

Cov.:

AF XY:

0.745

AC XY:

419120

AN XY:

562220

show subpopulations

Gnomad4 AFR exome

AF:

0.606

Gnomad4 AMR exome

AF:

0.748

Gnomad4 ASJ exome

AF:

0.747

Gnomad4 EAS exome

AF:

0.497

Gnomad4 SAS exome

AF:

0.735

Gnomad4 FIN exome

AF:

0.784

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.734

GnomAD4 genome

AF:

0.706

AC:

107363

AN:

151990

Hom.:

38508

Cov.:

AF XY:

0.707

AC XY:

52529

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.604

Gnomad4 AMR

AF:

0.711

Gnomad4 ASJ

AF:

0.750

Gnomad4 EAS

AF:

0.511

Gnomad4 SAS

AF:

0.727

Gnomad4 FIN

AF:

0.790

Gnomad4 NFE

AF:

0.764

Gnomad4 OTH

AF:

0.704

Alfa

AF:

0.744

Hom.:

19790

Bravo

AF:

0.698

Asia WGS

AF:

0.613

AC:

2133

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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