ENST00000330513.10:c.-202delT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000330513.10(TGIF1):c.-202delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,590,158 control chromosomes in the GnomAD database, including 123,175 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10520 hom., cov: 30)

Exomes 𝑓: 0.39 ( 112655 hom. )

Consequence

TGIF1
ENST00000330513.10 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.95

Publications

11 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

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 -16 ACMG points.

BP6

Variant 18-3452224-CT-C is Benign according to our data. Variant chr18-3452224-CT-C is described in ClinVar as Benign. ClinVar VariationId is 403532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGIF1	NM_003244.4 link	c.16+1720delT		intron_variant	Intron 1 of 2	ENST00000343820.10	NP_003235.1	Q15583-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGIF1	ENST00000343820.10 link	c.16+1720delT		intron_variant	Intron 1 of 2	1	NM_003244.4	ENSP00000339631.6		Q15583-2

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55004

AN:

151196

Hom.:

10512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.0156

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.380

GnomAD2 exomes

AF:

0.318

AC:

73899

AN:

232656

AF XY:

0.325

show subpopulations

Gnomad AFR exome

AF:

0.308

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.420

Gnomad EAS exome

AF:

0.0116

Gnomad FIN exome

AF:

0.387

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.390

AC:

561642

AN:

1438844

Hom.:

112655

Cov.:

AF XY:

0.388

AC XY:

277717

AN XY:

715418

show subpopulations

African (AFR)

AF:

0.329

AC:

10897

AN:

33080

American (AMR)

AF:

0.209

AC:

9267

AN:

44316

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

11179

AN:

25678

East Asian (EAS)

AF:

0.00859

AC:

340

AN:

39574

South Asian (SAS)

AF:

0.264

AC:

22585

AN:

85544

European-Finnish (FIN)

AF:

0.399

AC:

20811

AN:

52214

Middle Eastern (MID)

AF:

0.416

AC:

2321

AN:

5576

European-Non Finnish (NFE)

AF:

0.422

AC:

461474

AN:

1093450

Other (OTH)

AF:

0.383

AC:

22768

AN:

59412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

18198

36396

54594

72792

90990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13956

27912

41868

55824

69780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.364

AC:

55034

AN:

151314

Hom.:

10520

Cov.:

AF XY:

0.358

AC XY:

26444

AN XY:

73900

show subpopulations

African (AFR)

AF:

0.329

AC:

13556

AN:

41242

American (AMR)

AF:

0.303

AC:

4621

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1575

AN:

3460

East Asian (EAS)

AF:

0.0157

AC:

AN:

5168

South Asian (SAS)

AF:

0.246

AC:

1181

AN:

4798

European-Finnish (FIN)

AF:

0.404

AC:

4229

AN:

10478

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.422

AC:

28524

AN:

67614

Other (OTH)

AF:

0.379

AC:

795

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1544

3087

4631

6174

7718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.00693

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 542/2178=24.88% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.9

Mutation Taster

=119/81

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over