chr18-3449607-T-TGCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The XR_007066269.1(LOC124904237):​n.125+924_125+925insGGCGC variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 945,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

LOC124904237
XR_007066269.1 intron, non_coding_transcript

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.56
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 18-3449607-T-TGCGCC is Benign according to our data. Variant chr18-3449607-T-TGCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 3032359.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LOC124904237XR_007066269.1 linkuse as main transcriptn.125+924_125+925insGGCGC intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGIF1ENST00000549253.5 linkuse as main transcriptc.-83_-79dup 5_prime_UTR_variant 1/33
TGIF1ENST00000401449.5 linkuse as main transcriptc.-44-6736_-44-6732dup intron_variant 2 Q15583-4
TGIF1ENST00000548489.6 linkuse as main transcriptc.-44-6736_-44-6732dup intron_variant 3 Q15583-4

Frequencies

GnomAD3 genomes
AF:
0.0000355
AC:
4
AN:
112686
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000313
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000497
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000228
AC:
19
AN:
833148
Hom.:
0
Cov.:
36
AF XY:
0.0000234
AC XY:
9
AN XY:
384746
show subpopulations
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:
0.0000607
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000223
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000355
AC:
4
AN:
112686
Hom.:
0
Cov.:
31
AF XY:
0.0000586
AC XY:
3
AN XY:
51234
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000313
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000497
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

TGIF1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 15, 2020This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1393606991; hg19: chr18-3449605; API