rs3917201

Positions:

• chr14-75963212-C-T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.260

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFB3	NM_003239.5	c.926+104G>A		intron_variant		ENST00000238682.8
TGFB3	NM_001329938.2	c.*100G>A		3_prime_UTR_variant	5/5
TGFB3	NM_001329939.2	c.926+104G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFB3	ENST00000238682.8	c.926+104G>A		intron_variant		1	NM_003239.5	P1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107317 AN: 151872 Hom.: 38496 Cov.: 30

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.: 15 AF XY: 0.745 AC XY: 419120 AN XY: 562220

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.: 30 AF XY: 0.707 AC XY: 52529 AN XY: 74324

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	14
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

Other links and lift over

dbSNP: rs3917201; hg19: chr14-76429555; COSMIC: COSV53169360; COSMIC: COSV53169360;