Variant 18-3450457-C-A 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 NM_003244.4(TGIF1):c.-33C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,554,452 control chromosomes in the GnomAD database, including 26,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 8088 hom., cov: 32)

Exomes 𝑓: 0.14 ( 18256 hom. )

Consequence

TGIF1
NM_003244.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.311

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:

LOC124904237 (HGNC:):

LOC124904237 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 18-3450457-C-A is Benign according to our data. Variant chr18-3450457-C-A is described in ClinVar as [Benign]. Clinvar id is 259013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGIF1	NM_003244.4 linkuse as main transcript	c.-33C>A		5_prime_UTR_variant	1/3	ENST00000343820.10	NP_003235.1
LOC124904237	XR_007066269.1 linkuse as main transcript	n.125+75G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGIF1	ENST00000343820.10 linkuse as main transcript	c.-33C>A		5_prime_UTR_variant	1/3	1	NM_003244.4	ENSP00000339631	P1	Q15583-2

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39592

AN:

151956

Hom.:

8063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.576

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.160

AC:

25422

AN:

158684

Hom.:

3014

AF XY:

0.156

AC XY:

13108

AN XY:

84266

show subpopulations

Gnomad AFR exome

AF:

0.581

Gnomad AMR exome

AF:

0.0964

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.143

AC:

200669

AN:

1402378

Hom.:

18256

Cov.:

AF XY:

0.143

AC XY:

98621

AN XY:

692056

show subpopulations

Gnomad4 AFR exome

AF:

0.592

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.261

AC:

39670

AN:

152074

Hom.:

8088

Cov.:

AF XY:

0.259

AC XY:

19285

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.576

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.122

Hom.:

372

Bravo

AF:

0.270

Asia WGS

AF:

0.190

AC:

661

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Holoprosencephaly sequence

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.1

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

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