rs8082866

Variant names:

• chr18-3425213-T-A
• rs8082866
• NM_001278686.3:c.-45+6998T>A

Your query was ambiguous. Multiple possible variants found:

• chr18-3425213-T-A
• chr18-3425213-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001278686.3(TGIF1):​c.-45+6998T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: TGIF1 NM_001278686.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• holoprosencephaly 4

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ENSG00000302876 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGIF1	NM_001278686.3	c.-45+6998T>A		intron_variant	Intron 2 of 3		NP_001265615.1
TGIF1	NM_174886.3	c.-45+6998T>A		intron_variant	Intron 2 of 3		NP_777480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGIF1	ENST00000401449.5	c.-45+6998T>A		intron_variant	Intron 2 of 3	2		ENSP00000385206.1
TGIF1	ENST00000548489.6	c.-45+6998T>A		intron_variant	Intron 2 of 3	3		ENSP00000447747.2
TGIF1	ENST00000552383.5	c.-45+6998T>A		intron_variant	Intron 2 of 3	2		ENSP00000449287.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs8082866; hg19: chr18-3425211;