Genetic Variant TGIF1:c.-44-9000dupA (chr18-3447339-T-TA) – 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.-44-9000dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 11947 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:

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ACMG classification

Classification was made for transcript

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

BP6

Variant 18-3447339-T-TA is Benign according to our data. Variant chr18-3447339-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1280491.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 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.-44-9000dupA	intron	N/A	NP_001265615.1	Q15583-4
TGIF1	NM_174886.3	c.-44-9000dupA	intron	N/A	NP_777480.1	Q15583-4
TGIF1	NM_173207.4	c.-401_-400insA	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.-44-9015_-44-9014insA	intron	N/A	ENSP00000385206.1	Q15583-4
TGIF1	ENST00000548489.6	TSL:3	c.-44-9015_-44-9014insA	intron	N/A	ENSP00000447747.2	Q15583-4
TGIF1	ENST00000552383.5	TSL:2	c.-44-9015_-44-9014insA	intron	N/A	ENSP00000449287.1	F8VWK5

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

58635

AN:

141512

Hom.:

11947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.355

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.392

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

GnomAD4 genome

AF:

0.414

AC:

58634

AN:

141546

Hom.:

11947

Cov.:

AF XY:

0.409

AC XY:

27921

AN XY:

68264

show subpopulations

African (AFR)

AF:

0.419

AC:

16145

AN:

38540

American (AMR)

AF:

0.286

AC:

4035

AN:

14088

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1437

AN:

3366

East Asian (EAS)

AF:

0.229

AC:

1120

AN:

4898

South Asian (SAS)

AF:

0.340

AC:

1486

AN:

4376

European-Finnish (FIN)

AF:

0.461

AC:

3702

AN:

8030

Middle Eastern (MID)

AF:

0.349

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.454

AC:

29571

AN:

65126

Other (OTH)

AF:

0.390

AC:

766

AN:

1964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1624

3248

4872

6496

8120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.195

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 (auto)

(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