rs2020436

chr18-3448764-G-Achr18-3448764-G-C

Variant summary

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

The XR_007066269.1(LOC124904237):n.126-1578C>T 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 0.32 in 135,872 control chromosomes in the GnomAD database, including 7,728 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 0.32 (7728 hom., cov: 21)
• Consequence: LOC124904237 XR_007066269.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

Genes affected

LOC124904237 (HGNC:):

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904237	XR_007066269.1	n.126-1578C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGIF1	ENST00000401449.5	c.-44-7590G>A		intron_variant		2
TGIF1	ENST00000548489.6	c.-44-7590G>A		intron_variant		3
TGIF1	ENST00000549780.5	c.-45+167G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.320 AC: 43386 AN: 135790 Hom.: 7696 Cov.: 21

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.336

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.320 AC: 43449 AN: 135872 Hom.: 7728 Cov.: 21 AF XY: 0.326 AC XY: 21132 AN XY: 64852

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.318

Alfa AF: 0.254 Hom.: 6978

Bravo AF: 0.317

Asia WGS AF: 0.291 AC: 1002 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	7.0
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2020436; hg19: chr18-3448762;