18-3447727-C-T

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.-13C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,613,918 control chromosomes in the GnomAD database, including 1,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 527 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1429 hom. )

Consequence

TGIF1
NM_173207.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.453

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=-0.71).

BP6

Variant 18-3447727-C-T is Benign according to our data. Variant chr18-3447727-C-T is described in ClinVar as [Benign]. Clinvar id is 675019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TGIF1	NM_173207.4 link	c.-13C>T	5_prime_UTR_variant	Exon 1 of 3	NP_775299.1	Q15583-3
TGIF1	NM_001278686.3 link	c.-44-8627C>T	intron_variant	Intron 2 of 3	NP_001265615.1	Q15583-4
TGIF1	NM_174886.3 link	c.-44-8627C>T	intron_variant	Intron 2 of 3	NP_777480.1	Q15583-4
LOC124904237	XR_007066269.1 link	n.126-541G>A	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TGIF1	ENST00000618001 link	c.-13C>T	5_prime_UTR_variant	Exon 1 of 3	2	ENSP00000483499.1	Q15583-3
TGIF1	ENST00000401449.5 link	c.-44-8627C>T	intron_variant	Intron 2 of 3	2	ENSP00000385206.1	Q15583-4
TGIF1	ENST00000548489.6 link	c.-44-8627C>T	intron_variant	Intron 2 of 3	3	ENSP00000447747.2	Q15583-4

Frequencies

GnomAD3 genomes

AF:

0.0694

AC:

10550

AN:

152100

Hom.:

524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.0867

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0817

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0334

Gnomad OTH

AF:

0.0688

GnomAD3 exomes

AF:

0.0482

AC:

12110

AN:

251492

Hom.:

452

AF XY:

0.0461

AC XY:

6265

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.0255

Gnomad ASJ exome

AF:

0.0557

Gnomad EAS exome

AF:

0.0963

Gnomad SAS exome

AF:

0.0180

Gnomad FIN exome

AF:

0.0863

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0492

GnomAD4 exome

AF:

0.0380

AC:

55599

AN:

1461700

Hom.:

1429

Cov.:

AF XY:

0.0375

AC XY:

27250

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.0274

Gnomad4 ASJ exome

AF:

0.0597

Gnomad4 EAS exome

AF:

0.0779

Gnomad4 SAS exome

AF:

0.0198

Gnomad4 FIN exome

AF:

0.0835

Gnomad4 NFE exome

AF:

0.0320

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0694

AC:

10563

AN:

152218

Hom.:

527

Cov.:

AF XY:

0.0702

AC XY:

5226

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.0565

Gnomad4 EAS

AF:

0.0869

Gnomad4 SAS

AF:

0.0296

Gnomad4 FIN

AF:

0.0817

Gnomad4 NFE

AF:

0.0333

Gnomad4 OTH

AF:

0.0695

Alfa

AF:

0.0563

Hom.:

124

Bravo

AF:

0.0709

Asia WGS

AF:

0.0500

AC:

173

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

Jun 19, 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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.0

DANN

Benign

0.74

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