18-3412388-C-T

Position:

• chr18-3412388-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174886.3(TGIF1):​c.-118+134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,528 control chromosomes in the GnomAD database, including 6,651 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (6651 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGIF1 NM_174886.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGIF1	NM_174886.3	c.-118+134C>T		intron_variant			NP_777480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGIF1	ENST00000401449.5	c.-118+134C>T		intron_variant		2		ENSP00000385206
TGIF1	ENST00000552383.5	c.-118+134C>T		intron_variant		2		ENSP00000449287
TGIF1	ENST00000547233.1	n.51+134C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24534 AN: 151412 Hom.: 6623 Cov.: 33

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00476

Gnomad OTH AF: 0.134

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.162 AC: 24611 AN: 151528 Hom.: 6651 Cov.: 33 AF XY: 0.157 AC XY: 11620 AN XY: 74110

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.0701

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00476

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0987 Hom.: 503

Bravo AF: 0.186

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8092903; hg19: chr18-3412386;