18-3447963-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173207.4(TGIF1):c.58+166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 886,368 control chromosomes in the GnomAD database, including 1,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 622 hom., cov: 30)

Exomes 𝑓: 0.017 ( 389 hom. )

Consequence

TGIF1
NM_173207.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0430

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 links:

LOC124904237 (HGNC:):

LOC124904237 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 18-3447963-A-G is Benign according to our data. Variant chr18-3447963-A-G is described in ClinVar as [Benign]. Clinvar id is 672771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TGIF1	NM_173207.4 link	c.58+166A>G	intron_variant	Intron 1 of 2	NP_775299.1	Q15583-3
TGIF1	NM_001278686.3 link	c.-44-8391A>G	intron_variant	Intron 2 of 3	NP_001265615.1	Q15583-4
TGIF1	NM_174886.3 link	c.-44-8391A>G	intron_variant	Intron 2 of 3	NP_777480.1	Q15583-4
LOC124904237	XR_007066269.1 link	n.126-777T>C	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TGIF1	ENST00000618001.4 link	c.58+166A>G	intron_variant	Intron 1 of 2	2	ENSP00000483499.1	Q15583-3
TGIF1	ENST00000401449.5 link	c.-44-8391A>G	intron_variant	Intron 2 of 3	2	ENSP00000385206.1	Q15583-4
TGIF1	ENST00000548489.6 link	c.-44-8391A>G	intron_variant	Intron 2 of 3	3	ENSP00000447747.2	Q15583-4

Frequencies

GnomAD3 genomes

AF:

0.0590

AC:

8935

AN:

151466

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.00774

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.00276

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0509

GnomAD4 exome

AF:

0.0170

AC:

12515

AN:

734784

Hom.:

389

AF XY:

0.0164

AC XY:

5610

AN XY:

341408

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.0168

Gnomad4 ASJ exome

AF:

0.0188

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.0393

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.0351

GnomAD4 genome

AF:

0.0591

AC:

8956

AN:

151584

Hom.:

622

Cov.:

AF XY:

0.0603

AC XY:

4464

AN XY:

74052

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.0277

Gnomad4 ASJ

AF:

0.0188

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.0399

Gnomad4 FIN

AF:

0.00276

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.0494

Alfa

AF:

0.0302

Hom.:

Bravo

AF:

0.0662

Asia WGS

AF:

0.106

AC:

367

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.6

DANN

Benign

0.50

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over