14-28767055-CTTTTTTT-CTTTTT

Variant names:

• chr14-28767055-CTT-C
• rs542787885
• NM_005249.5:c.-211_-210delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005249.5(FOXG1):​c.-211_-210delTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 143,100 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0053 (0 hom.)
• Consequence: FOXG1 NM_005249.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

Genes affected

FOXG1 (HGNC:3811): (forkhead box G1) This locus encodes a member of the fork-head transcription factor family. The encoded protein, which functions as a transcriptional repressor, is highly expressed in neural tissues during brain development. Mutations at this locus have been associated with Rett syndrome and a diverse spectrum of neurodevelopmental disorders defined as part of the FOXG1 syndrome. This gene is disregulated in many types of cancer and is the target of multiple microRNAs that regulate the proliferation of tumor cells. [provided by RefSeq, Jul 2020]

LINC01551 (HGNC:19828): (long intergenic non-protein coding RNA 1551)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00526 (18/3420) while in subpopulation EAS AF= 0.0357 (1/28). AF 95% confidence interval is 0.00423. There are 0 homozygotes in gnomad4_exome. There are 11 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5	c.-211_-210delTT		5_prime_UTR_variant	Exon 1 of 1	ENST00000313071.7	NP_005240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXG1	ENST00000313071	c.-211_-210delTT		5_prime_UTR_variant	Exon 1 of 1		NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482	c.-211_-210delTT		5_prime_UTR_variant	Exon 2 of 2			ENSP00000516406.1
LINC01551	ENST00000675861.1	n.374+1056_374+1057delTT		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.000122 AC: 17 AN: 139680 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000418

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000711

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00526 AC: 18 AN: 3420 Hom.: 0 AF XY: 0.00561 AC XY: 11 AN XY: 1962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0357

Gnomad4 SAS exome AF: 0.0107

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00478

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000122 AC: 17 AN: 139680 Hom.: 0 Cov.: 29 AF XY: 0.000148 AC XY: 10 AN XY: 67590

Gnomad4 AFR AF: 0.000418

Gnomad4 AMR AF: 0.0000711

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs542787885; hg19: chr14-29236261;