chr18-3452224-CT-C

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

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

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

Dec 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter