Variant chr18-3451764-C-T 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.-663C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,250,686 control chromosomes in the GnomAD database, including 9,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2258 hom., cov: 32)

Exomes 𝑓: 0.10 ( 6826 hom. )

Consequence

TGIF1
ENST00000330513.10 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0160

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 18-3451764-C-T is Benign according to our data. Variant chr18-3451764-C-T is described in ClinVar as [Benign]. Clinvar id is 675145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 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+1259C>T		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+1259C>T		intron_variant		1	NM_003244.4	P1	Q15583-2

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23086

AN:

152008

Hom.:

2247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0968

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.0602

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.0990

Gnomad OTH

AF:

0.150

GnomAD4 exome

AF:

0.104

AC:

114744

AN:

1098560

Hom.:

6826

Cov.:

AF XY:

0.104

AC XY:

54240

AN XY:

520120

show subpopulations

Gnomad4 AFR exome

AF:

0.275

Gnomad4 AMR exome

AF:

0.0887

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.0666

Gnomad4 NFE exome

AF:

0.0950

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.152

AC:

23127

AN:

152126

Hom.:

2258

Cov.:

AF XY:

0.152

AC XY:

11310

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.0965

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.0602

Gnomad4 NFE

AF:

0.0990

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.110

Hom.:

1458

Bravo

AF:

0.158

Asia WGS

AF:

0.201

AC:

700

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 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

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.0

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.35

Position offset: -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