18-3451390-C-CAA

Position:

• chr18-3451390-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003244.4(TGIF1):​c.16+886_16+887insAA variant causes a intron change. The variant allele was found at a frequency of 0.074 in 985,296 control chromosomes in the GnomAD database, including 4,111 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1958 hom., cov: 30)
  • Exomes 𝑓: 0.064 (2153 hom.)
• Consequence: TGIF1 NM_003244.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.76

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 -10 ACMG points.

• BP6: Variant 18-3451390-C-CAA is Benign according to our data. Variant chr18-3451390-C-CAA is described in ClinVar as [Benign]. Clinvar id is 1245973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGIF1	NM_003244.4	c.16+886_16+887insAA		intron_variant		ENST00000343820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGIF1	ENST00000343820.10	c.16+886_16+887insAA		intron_variant		1	NM_003244.4	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19825 AN: 152106 Hom.: 1937 Cov.: 30

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0782

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0636 AC: 53023 AN: 833072 Hom.: 2153 Cov.: 28 AF XY: 0.0631 AC XY: 24258 AN XY: 384702

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.0732

Gnomad4 ASJ exome AF: 0.0877

Gnomad4 EAS exome AF: 0.0821

Gnomad4 SAS exome AF: 0.0733

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0578

Gnomad4 OTH exome AF: 0.0735

GnomAD4 genome AF: 0.131 AC: 19880 AN: 152224 Hom.: 1958 Cov.: 30 AF XY: 0.132 AC XY: 9819 AN XY: 74448

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.0779

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.0812

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0314 Hom.: 22

Bravo AF: 0.134

Asia WGS AF: 0.0730 AC: 254 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, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141177192; hg19: chr18-3451388;