18-3447339-TA-T

Position:

• chr18-3447339-TA-T

Variant summary

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

The XR_007066269.1(LOC124904237):​n.126-154del 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 0.023 (86 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-TA-T is Benign according to our data. Variant chr18-3447339-TA-T is described in ClinVar as [Benign]. Clinvar id is 1282084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904237	XR_007066269.1	n.126-154del		intron_variant, non_coding_transcript_variant
TGIF1	NM_001278686.3	c.-44-9000del		intron_variant			NP_001265615.1
TGIF1	NM_174886.3	c.-44-9000del		intron_variant			NP_777480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGIF1	ENST00000401449.5	c.-44-9000del		intron_variant		2		ENSP00000385206
TGIF1	ENST00000548489.6	c.-44-9000del		intron_variant		3		ENSP00000447747
TGIF1	ENST00000550958.5	c.-44-9000del		intron_variant		3		ENSP00000449531
TGIF1	ENST00000552383.5	c.-44-9000del		intron_variant		2		ENSP00000449287

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3185 AN: 141544 Hom.: 86 Cov.: 0

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00594

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.00849

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.0190

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

GnomAD4 genome AF: 0.0225 AC: 3190 AN: 141580 Hom.: 86 Cov.: 0 AF XY: 0.0222 AC XY: 1516 AN XY: 68250

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00594

Gnomad4 EAS AF: 0.0302

Gnomad4 SAS AF: 0.0171

Gnomad4 FIN AF: 0.00849

Gnomad4 NFE AF: 0.00256

Gnomad4 OTH AF: 0.0194

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

Aug 20, 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;