18-3447339-T-TA

Position:

• chr18-3447339-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The XR_007066269.1(LOC124904237):​n.126-154_126-153insT variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (11947 hom., cov: 0)
• Consequence: LOC124904237 XR_007066269.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.266

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 -10 ACMG points.

• BP6: Variant 18-3447339-T-TA is Benign according to our data. Variant chr18-3447339-T-TA is described in ClinVar as [Benign]. Clinvar id is 1280491.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904237	XR_007066269.1	n.126-154_126-153insT		intron_variant, non_coding_transcript_variant
TGIF1	NM_001278686.3	c.-44-9000dup		intron_variant
TGIF1	NM_174886.3	c.-44-9000dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGIF1	ENST00000401449.5	c.-44-9000dup		intron_variant		2
TGIF1	ENST00000548489.6	c.-44-9000dup		intron_variant		3
TGIF1	ENST00000550958.5	c.-44-9000dup		intron_variant		3
TGIF1	ENST00000552383.5	c.-44-9000dup		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 58635 AN: 141512 Hom.: 11947 Cov.: 0

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.355

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.414 AC: 58634 AN: 141546 Hom.: 11947 Cov.: 0 AF XY: 0.409 AC XY: 27921 AN XY: 68264

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.390

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11421150; hg19: chr18-3447337;