Variant chr18-3451541-GA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_003244.4(TGIF1):c.16+1037del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 1,008,350 control chromosomes in the GnomAD database, including 4,204 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.074 ( 443 hom., cov: 31)

Exomes 𝑓: 0.093 ( 3761 hom. )

Consequence

TGIF1
NM_003244.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.211

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 -10 ACMG points.

BP6

Variant 18-3451541-GA-G is Benign according to our data. Variant chr18-3451541-GA-G is described in ClinVar as [Benign]. Clinvar id is 674962.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0885 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+1037del		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+1037del		intron_variant		1	NM_003244.4	P1	Q15583-2

Frequencies

GnomAD3 genomes

AF:

0.0744

AC:

11325

AN:

152150

Hom.:

440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0576

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0656

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.0139

Gnomad SAS

AF:

0.0771

Gnomad FIN

AF:

0.0518

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0903

Gnomad OTH

AF:

0.0755

GnomAD4 exome

AF:

0.0926

AC:

79256

AN:

856082

Hom.:

3761

Cov.:

AF XY:

0.0925

AC XY:

36655

AN XY:

396266

show subpopulations

Gnomad4 AFR exome

AF:

0.0524

Gnomad4 AMR exome

AF:

0.0353

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.0118

Gnomad4 SAS exome

AF:

0.0782

Gnomad4 FIN exome

AF:

0.0481

Gnomad4 NFE exome

AF:

0.0942

Gnomad4 OTH exome

AF:

0.0934

GnomAD4 genome

AF:

0.0745

AC:

11338

AN:

152268

Hom.:

443

Cov.:

AF XY:

0.0719

AC XY:

5355

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0576

Gnomad4 AMR

AF:

0.0655

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.0139

Gnomad4 SAS

AF:

0.0766

Gnomad4 FIN

AF:

0.0518

Gnomad4 NFE

AF:

0.0904

Gnomad4 OTH

AF:

0.0790

Bravo

AF:

0.0740

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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