rs113866405

Variant names:

• chr18-3447827-C-G
• rs113866405
• NM_173207.4:c.58+30C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-3447827-C-G
• chr18-3447827-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_173207.4(TGIF1):​c.58+30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000697 in 1,613,866 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (7 hom.)
• Consequence: TGIF1 NM_173207.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0100
• Publications: 0 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: PanelApp Australia, Laboratory for Molecular Medicine, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000302876 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 18-3447827-C-G is Benign according to our data. Variant chr18-3447827-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1204789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 578 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173207.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGIF1	NM_173207.4		c.58+30C>G		intron	N/A	NP_775299.1	Q15583-3
	TGIF1	NM_001278686.3		c.-44-8527C>G		intron	N/A	NP_001265615.1	Q15583-4
	TGIF1	NM_174886.3		c.-44-8527C>G		intron	N/A	NP_777480.1	Q15583-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGIF1	ENST00000618001.4	TSL:2	c.58+30C>G		intron	N/A	ENSP00000483499.1	Q15583-3
	TGIF1	ENST00000401449.5	TSL:2	c.-44-8527C>G		intron	N/A	ENSP00000385206.1	Q15583-4
	TGIF1	ENST00000548489.6	TSL:3	c.-44-8527C>G		intron	N/A	ENSP00000447747.2	Q15583-4

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 580 AN: 152136 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000994 AC: 250 AN: 251450 AF XY: 0.000684

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000374 AC: 547 AN: 1461612 Hom.: 7 Cov.: 30 AF XY: 0.000347 AC XY: 252 AN XY: 727146

African (AFR) AF: 0.0123 AC: 412 AN: 33474

American (AMR) AF: 0.000894 AC: 40 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111754

Other (OTH) AF: 0.00114 AC: 69 AN: 60394

GnomAD4 genome AF: 0.00380 AC: 578 AN: 152254 Hom.: 4 Cov.: 32 AF XY: 0.00359 AC XY: 267 AN XY: 74446

African (AFR) AF: 0.0134 AC: 555 AN: 41548

American (AMR) AF: 0.00111 AC: 17 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.00434

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.2
DANN	Benign	0.28
PhyloP100		0.010
PromoterAI		-0.16	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs113866405; hg19: chr18-3447825;