Variant chr18-3452224-CT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000330513.10(TGIF1):c.-202del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,590,158 control chromosomes in the GnomAD database, including 123,175 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10520 hom., cov: 30)

Exomes 𝑓: 0.39 ( 112655 hom. )

Consequence

TGIF1
ENST00000330513.10 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.95

Variant links:

Genes affected

TGIF1 (HGNC:11776): (TGFB induced factor homeobox 1) The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]

TGIF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 18-3452224-CT-C is Benign according to our data. Variant chr18-3452224-CT-C is described in ClinVar as [Benign]. Clinvar id is 403532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3452224-CT-C is described in Lovd as [Benign]. Variant chr18-3452224-CT-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGIF1	NM_003244.4 linkuse as main transcript	c.16+1720del		intron_variant		ENST00000343820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGIF1	ENST00000343820.10 linkuse as main transcript	c.16+1720del		intron_variant		1	NM_003244.4	P1	Q15583-2

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55004

AN:

151196

Hom.:

10512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.0156

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.380

GnomAD3 exomes

AF:

0.318

AC:

73899

AN:

232656

Hom.:

12428

AF XY:

0.325

AC XY:

41340

AN XY:

127308

show subpopulations

Gnomad AFR exome

AF:

0.308

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.420

Gnomad EAS exome

AF:

0.0116

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.387

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.390

AC:

561642

AN:

1438844

Hom.:

112655

Cov.:

AF XY:

0.388

AC XY:

277717

AN XY:

715418

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.209

Gnomad4 ASJ exome

AF:

0.435

Gnomad4 EAS exome

AF:

0.00859

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.399

Gnomad4 NFE exome

AF:

0.422

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.364

AC:

55034

AN:

151314

Hom.:

10520

Cov.:

AF XY:

0.358

AC XY:

26444

AN XY:

73900

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.0157

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.422

Gnomad4 OTH

AF:

0.379

Alfa

AF:

0.00693

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 11, 2019	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 542/2178=24.88% -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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