Genetic Variant TGIF1:c.-44-9000delA (chr18-3447339-TA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_174886.3(TGIF1):c.-44-9000delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 86 hom., cov: 0)

Consequence

TGIF1
NM_174886.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.266

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

holoprosencephaly 4
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

TGIF1 links:

ENSG00000302876 (HGNC:):

ENSG00000302876 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 18-3447339-TA-T is Benign according to our data. Variant chr18-3447339-TA-T is described in ClinVar as Benign. ClinVar VariationId is 1282084.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174886.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
TGIF1	NM_001278686.3	c.-44-9000delA	intron	N/A	NP_001265615.1	Q15583-4
TGIF1	NM_174886.3	c.-44-9000delA	intron	N/A	NP_777480.1	Q15583-4
TGIF1	NM_173207.4	c.-400delA	upstream_gene	N/A	NP_775299.1	Q15583-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TGIF1	ENST00000401449.5	TSL:2	c.-44-9014delA	intron	N/A	ENSP00000385206.1	Q15583-4
TGIF1	ENST00000548489.6	TSL:3	c.-44-9014delA	intron	N/A	ENSP00000447747.2	Q15583-4
TGIF1	ENST00000552383.5	TSL:2	c.-44-9014delA	intron	N/A	ENSP00000449287.1	F8VWK5

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3185

AN:

141544

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.00594

Gnomad EAS

AF:

0.0299

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00849

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.00256

Gnomad OTH

AF:

0.0190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0225

AC:

3190

AN:

141580

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

1516

AN XY:

68250

show subpopulations

African (AFR)

AF:

0.0652

AC:

2517

AN:

38584

American (AMR)

AF:

0.0109

AC:

154

AN:

14074

Ashkenazi Jewish (ASJ)

AF:

0.00594

AC:

AN:

3366

East Asian (EAS)

AF:

0.0302

AC:

148

AN:

4900

South Asian (SAS)

AF:

0.0171

AC:

AN:

4388

European-Finnish (FIN)

AF:

0.00849

AC:

AN:

8014

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00256

AC:

167

AN:

65134

Other (OTH)

AF:

0.0194

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

125

250

375

500

625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000622

Hom.:

416

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over