rs1393606991

Variant names:

• chr18-3449607-TGCGCC-T
• rs1393606991
• NM_001278682.2:c.-14_-10delGCGCC

Your query was ambiguous. Multiple possible variants found:

• chr18-3449607-TGCGCC-T
• chr18-3449607-TGCGCC-TGCGCCGCGCC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

The NM_001278682.2(TGIF1):​c.-14_-10delGCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000006 in 833,148 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: TGIF1 NM_001278682.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGIF1	NM_001278682.2	c.-14_-10delGCGCC		5_prime_UTR_variant	Exon 1 of 3		NP_001265611.1
TGIF1	NM_173207.4	c.58+1821_58+1825delGCGCC		intron_variant	Intron 1 of 2		NP_775299.1
TGIF1	NM_001278686.3	c.-44-6736_-44-6732delGCGCC		intron_variant	Intron 2 of 3		NP_001265615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGIF1	ENST00000549253.5	c.-83_-79delGCGCC		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000449973.1
TGIF1	ENST00000618001.4	c.58+1821_58+1825delGCGCC		intron_variant	Intron 1 of 2	2		ENSP00000483499.1
TGIF1	ENST00000401449.5	c.-44-6736_-44-6732delGCGCC		intron_variant	Intron 2 of 3	2		ENSP00000385206.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000600 AC: 5 AN: 833148 Hom.: 0 AF XY: 0.00000780 AC XY: 3 AN XY: 384746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000656

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

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: rs1393606991; hg19: chr18-3449605;