18-3450206-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003244.4(TGIF1):c.-284A>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 0.00502 in 1,378,062 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (146 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (115 hom.)
• Consequence: TGIF1 NM_003244.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.363

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]

LOC124904237 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 18-3450206-A-T is Benign according to our data. Variant chr18-3450206-A-T is described in ClinVar as [Benign]. Clinvar id is 1232556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGIF1	NM_003244.4	c.-284A>T		5_prime_UTR_variant	1/3	ENST00000343820.10
LOC124904237	XR_007066269.1	n.125+326T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGIF1	ENST00000343820.10	c.-284A>T		5_prime_UTR_variant	1/3	1	NM_003244.4	P1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3813 AN: 152140 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.00252 AC: 3087 AN: 1225804 Hom.: 115 Cov.: 29 AF XY: 0.00230 AC XY: 1358 AN XY: 591198

Gnomad4 AFR exome AF: 0.0858

Gnomad4 AMR exome AF: 0.00780

Gnomad4 ASJ exome AF: 0.00230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000244

Gnomad4 OTH exome AF: 0.00646

GnomAD4 genome AF: 0.0251 AC: 3829 AN: 152258 Hom.: 146 Cov.: 32 AF XY: 0.0246 AC XY: 1829 AN XY: 74456

Gnomad4 AFR AF: 0.0857

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.000863 Hom.: 0

Bravo AF: 0.0279

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	12
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7233448; hg19: chr18-3450204;