18-3447873-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173207.4(TGIF1):c.58+76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,577,428 control chromosomes in the GnomAD database, including 382,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42143 hom., cov: 29)

Exomes 𝑓: 0.68 ( 340659 hom. )

Consequence

TGIF1
NM_173207.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.362

Publications

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

TGIF1 links:

ENSG00000302876 (HGNC:):

ENSG00000302876 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_173207.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 18-3447873-T-C is Benign according to our data. Variant chr18-3447873-T-C is described in ClinVar as Benign. ClinVar VariationId is 674961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173207.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
TGIF1	NM_173207.4	c.58+76T>C	intron	N/A	NP_775299.1	Q15583-3
TGIF1	NM_001278686.3	c.-44-8481T>C	intron	N/A	NP_001265615.1	Q15583-4
TGIF1	NM_174886.3	c.-44-8481T>C	intron	N/A	NP_777480.1	Q15583-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TGIF1	ENST00000618001.4	TSL:2	c.58+76T>C	intron	N/A	ENSP00000483499.1	Q15583-3
TGIF1	ENST00000401449.5	TSL:2	c.-44-8481T>C	intron	N/A	ENSP00000385206.1	Q15583-4
TGIF1	ENST00000548489.6	TSL:3	c.-44-8481T>C	intron	N/A	ENSP00000447747.2	Q15583-4

Frequencies

GnomAD3 genomes

AF:

0.733

AC:

111171

AN:

151618

Hom.:

42105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.913

Gnomad AMI

AF:

0.640

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.693

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.464

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.675

Gnomad NFE

AF:

0.702

Gnomad OTH

AF:

0.717

GnomAD4 exome

AF:

0.685

AC:

976375

AN:

1425690

Hom.:

340659

AF XY:

0.679

AC XY:

482989

AN XY:

711436

show subpopulations

African (AFR)

AF:

0.924

AC:

30283

AN:

32774

American (AMR)

AF:

0.504

AC:

22433

AN:

44542

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

17971

AN:

25944

East Asian (EAS)

AF:

0.428

AC:

16916

AN:

39492

South Asian (SAS)

AF:

0.480

AC:

41031

AN:

85476

European-Finnish (FIN)

AF:

0.715

AC:

38151

AN:

53342

Middle Eastern (MID)

AF:

0.665

AC:

3785

AN:

5694

European-Non Finnish (NFE)

AF:

0.710

AC:

765863

AN:

1079198

Other (OTH)

AF:

0.674

AC:

39942

AN:

59228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

15586

31171

46757

62342

77928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18892

37784

56676

75568

94460

<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:

0.733

AC:

111260

AN:

151738

Hom.:

42143

Cov.:

AF XY:

0.727

AC XY:

53906

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.913

AC:

37767

AN:

41388

American (AMR)

AF:

0.617

AC:

9395

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

2405

AN:

3468

East Asian (EAS)

AF:

0.409

AC:

2100

AN:

5140

South Asian (SAS)

AF:

0.464

AC:

2215

AN:

4770

European-Finnish (FIN)

AF:

0.706

AC:

7415

AN:

10506

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.702

AC:

47683

AN:

67926

Other (OTH)

AF:

0.713

AC:

1501

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1401

2802

4202

5603

7004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.717

Hom.:

44478

Bravo

AF:

0.735

Asia WGS

AF:

0.423

AC:

1475

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.4

(source)

DANN

Benign

0.39

PhyloP100

0.36

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=19/81

disease causing

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over