rs2229337

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003244.4(TGIF1):c.420A>G(p.Pro140Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 1,613,952 control chromosomes in the GnomAD database, including 9,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2259 hom., cov: 32)

Exomes 𝑓: 0.083 ( 7007 hom. )

Consequence

TGIF1
NM_003244.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.40

Publications

14 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 18-3457541-A-G is Benign according to our data. Variant chr18-3457541-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGIF1	NM_003244.4 link	c.420A>G	p.Pro140Pro	synonymous_variant	Exon 3 of 3	ENST00000343820.10	NP_003235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGIF1	ENST00000343820.10 link	c.420A>G	p.Pro140Pro	synonymous_variant	Exon 3 of 3	1	NM_003244.4	ENSP00000339631.6

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21087

AN:

151952

Hom.:

2258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.0803

Gnomad ASJ

AF:

0.0835

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0691

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.102

AC:

25699

AN:

251440

AF XY:

0.0998

show subpopulations

Gnomad AFR exome

AF:

0.292

Gnomad AMR exome

AF:

0.0483

Gnomad ASJ exome

AF:

0.0879

Gnomad EAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.0496

Gnomad NFE exome

AF:

0.0690

Gnomad OTH exome

AF:

0.0868

GnomAD4 exome

AF:

0.0826

AC:

120775

AN:

1461882

Hom.:

7007

Cov.:

AF XY:

0.0831

AC XY:

60402

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.298

AC:

9985

AN:

33480

American (AMR)

AF:

0.0530

AC:

2369

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0913

AC:

2386

AN:

26136

East Asian (EAS)

AF:

0.267

AC:

10612

AN:

39698

South Asian (SAS)

AF:

0.121

AC:

10412

AN:

86258

European-Finnish (FIN)

AF:

0.0489

AC:

2613

AN:

53420

Middle Eastern (MID)

AF:

0.140

AC:

809

AN:

5768

European-Non Finnish (NFE)

AF:

0.0678

AC:

75394

AN:

1112006

Other (OTH)

AF:

0.103

AC:

6195

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7730

15461

23191

30922

38652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3084

6168

9252

12336

15420

<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:

0.139

AC:

21110

AN:

152070

Hom.:

2259

Cov.:

AF XY:

0.138

AC XY:

10235

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.288

AC:

11945

AN:

41430

American (AMR)

AF:

0.0801

AC:

1224

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0835

AC:

290

AN:

3472

East Asian (EAS)

AF:

0.277

AC:

1431

AN:

5166

South Asian (SAS)

AF:

0.126

AC:

607

AN:

4814

European-Finnish (FIN)

AF:

0.0488

AC:

517

AN:

10586

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0691

AC:

4701

AN:

68002

Other (OTH)

AF:

0.129

AC:

273

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

870

1740

2609

3479

4349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.106

Hom.:

669

Bravo

AF:

0.147

Asia WGS

AF:

0.190

AC:

662

AN:

3478

EpiCase

AF:

0.0760

EpiControl

AF:

0.0784

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Holoprosencephaly 4

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Holoprosencephaly sequence

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.035

(source)

DANN

Benign

0.19

PhyloP100

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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