chr18-3448073-C-CG

Position:

• chr18-3448073-C-CG

Variant summary

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

The XR_007066269.1(LOC124904237):​n.126-888_126-887insC variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 947,416 control chromosomes in the GnomAD database, including 1,841 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (1221 hom., cov: 29)
  • Exomes 𝑓: 0.022 (620 hom.)
• Consequence: LOC124904237 XR_007066269.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53

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 18-3448073-C-CG is Benign according to our data. Variant chr18-3448073-C-CG is described in ClinVar as [Benign]. Clinvar id is 1288921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904237	XR_007066269.1	n.126-888_126-887insC		intron_variant, non_coding_transcript_variant
TGIF1	NM_001278686.3	c.-44-8273dup		intron_variant
TGIF1	NM_173207.4	c.58+284dup		intron_variant
TGIF1	NM_174886.3	c.-44-8273dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGIF1	ENST00000401449.5	c.-44-8273dup		intron_variant		2
TGIF1	ENST00000548489.6	c.-44-8273dup		intron_variant		3
TGIF1	ENST00000550958.5	c.-44-8273dup		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0840 AC: 11863 AN: 141240 Hom.: 1214 Cov.: 29

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0751

Gnomad EAS AF: 0.00569

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.00374

Gnomad MID AF: 0.0882

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0777

GnomAD4 exome AF: 0.0219 AC: 17661 AN: 806052 Hom.: 620 Cov.: 29 AF XY: 0.0217 AC XY: 8104 AN XY: 372670

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.0278

Gnomad4 ASJ exome AF: 0.0765

Gnomad4 EAS exome AF: 0.00490

Gnomad4 SAS exome AF: 0.0176

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0162

Gnomad4 OTH exome AF: 0.0324

GnomAD4 genome AF: 0.0842 AC: 11900 AN: 141364 Hom.: 1221 Cov.: 29 AF XY: 0.0812 AC XY: 5560 AN XY: 68492

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.0477

Gnomad4 ASJ AF: 0.0751

Gnomad4 EAS AF: 0.00570

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.00374

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0815

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

Oct 30, 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: rs34135793; hg19: chr18-3448071;