rs11571510

Variant names:

• chr18-3452224-CT-C
• rs11571510
• ENST00000330513.10:c.-202delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_170695.5(TGIF1):​c.-202delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,590,158 control chromosomes in the GnomAD database, including 123,175 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10520 hom., cov: 30)
  • Exomes 𝑓: 0.39 (112655 hom.)
• Consequence: TGIF1 NM_170695.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.95
• Publications: 11 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, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, G2P

ENSG00000302876 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 18-3452224-CT-C is Benign according to our data. Variant chr18-3452224-CT-C is described in ClinVar as Benign. ClinVar VariationId is 403532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170695.5. 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_003244.4	MANE Select	c.16+1720delT		intron	N/A	NP_003235.1	Q15583-2
	TGIF1	NM_170695.5		c.-202delT		5_prime_UTR	Exon 1 of 3	NP_733796.3
	TGIF1	NM_173207.4		c.59-4129delT		intron	N/A	NP_775299.1	Q15583-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGIF1	ENST00000330513.10	TSL:1	c.-202delT		5_prime_UTR	Exon 1 of 3	ENSP00000327959.6	Q15583-4
	TGIF1	ENST00000343820.10	TSL:1 MANE Select	c.16+1720delT		intron	N/A	ENSP00000339631.6	Q15583-2
	TGIF1	ENST00000618001.4	TSL:2	c.59-4129delT		intron	N/A	ENSP00000483499.1	Q15583-3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55004 AN: 151196 Hom.: 10512 Cov.: 30

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.380

GnomAD2 exomes AF: 0.318 AC: 73899 AN: 232656 AF XY: 0.325

Gnomad AFR exome AF: 0.308

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.0116

Gnomad FIN exome AF: 0.387

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.390 AC: 561642 AN: 1438844 Hom.: 112655 Cov.: 0 AF XY: 0.388 AC XY: 277717 AN XY: 715418

African (AFR) AF: 0.329 AC: 10897 AN: 33080

American (AMR) AF: 0.209 AC: 9267 AN: 44316

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11179 AN: 25678

East Asian (EAS) AF: 0.00859 AC: 340 AN: 39574

South Asian (SAS) AF: 0.264 AC: 22585 AN: 85544

European-Finnish (FIN) AF: 0.399 AC: 20811 AN: 52214

Middle Eastern (MID) AF: 0.416 AC: 2321 AN: 5576

European-Non Finnish (NFE) AF: 0.422 AC: 461474 AN: 1093450

Other (OTH) AF: 0.383 AC: 22768 AN: 59412

GnomAD4 genome AF: 0.364 AC: 55034 AN: 151314 Hom.: 10520 Cov.: 30 AF XY: 0.358 AC XY: 26444 AN XY: 73900

African (AFR) AF: 0.329 AC: 13556 AN: 41242

American (AMR) AF: 0.303 AC: 4621 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1575 AN: 3460

East Asian (EAS) AF: 0.0157 AC: 81 AN: 5168

South Asian (SAS) AF: 0.246 AC: 1181 AN: 4798

European-Finnish (FIN) AF: 0.404 AC: 4229 AN: 10478

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28524 AN: 67614

Other (OTH) AF: 0.379 AC: 795 AN: 2100

Alfa AF: 0.00693 Hom.: 9

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.9
Mutation Taster		=119/81	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11571510;

hg19: chr18-3452222;

COSMIC: COSV57906818;

COSMIC: COSV57906818;