18-3415833-C-T

Variant names:

• chr18-3415833-C-T
• rs12457997

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.573 in 151,952 control chromosomes in the GnomAD database, including 26,908 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 0.57 (26908 hom., cov: 32)
• Consequence: BOD1P1 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 6 publications found

Genes affected

BOD1P1 (HGNC:51435): (biorientation of chromosomes in cell division 1 pseudogene 1)

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000401449.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGIF1	NM_001278686.3		c.-117-2310C>T		intron	N/A	NP_001265615.1
	TGIF1	NM_174886.3		c.-117-2310C>T		intron	N/A	NP_777480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGIF1	ENST00000401449.5	TSL:2	c.-117-2310C>T		intron	N/A	ENSP00000385206.1
	TGIF1	ENST00000548489.6	TSL:3	c.-117-2310C>T		intron	N/A	ENSP00000447747.2
	TGIF1	ENST00000552383.5	TSL:2	c.-117-2310C>T		intron	N/A	ENSP00000449287.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86998 AN: 151834 Hom.: 26898 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.573 AC: 87022 AN: 151952 Hom.: 26908 Cov.: 32 AF XY: 0.577 AC XY: 42821 AN XY: 74250

African (AFR) AF: 0.317 AC: 13133 AN: 41384

American (AMR) AF: 0.687 AC: 10491 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2410 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3578 AN: 5170

South Asian (SAS) AF: 0.648 AC: 3121 AN: 4816

European-Finnish (FIN) AF: 0.672 AC: 7094 AN: 10552

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45169 AN: 67980

Other (OTH) AF: 0.607 AC: 1278 AN: 2104

Alfa AF: 0.637 Hom.: 138372

Bravo AF: 0.564

Asia WGS AF: 0.666 AC: 2317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	16
DANN	Benign	0.66
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12457997; hg19: chr18-3415831;