14-28767055-CTTTTTTT-CTTTTTTTTT

Variant names:

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

Variant summary

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

The NM_005249.5(FOXG1):​c.-211_-210dupTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 143,134 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 0.000057 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: FOXG1 NM_005249.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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 nfe. gnomad4_exome allele frequency = 0.00232 (8/3448) while in subpopulation NFE AF= 0.00276 (7/2532). AF 95% confidence interval is 0.0013. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000501 AC: 7 AN: 139686 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000523

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000304

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00704

Gnomad NFE AF: 0.0000312

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00232 AC: 8 AN: 3448 Hom.: 0 Cov.: 0 AF XY: 0.00355 AC XY: 7 AN XY: 1974

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00214

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00276

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000573 AC: 8 AN: 139686 Hom.: 0 Cov.: 29 AF XY: 0.0000444 AC XY: 3 AN XY: 67606

Gnomad4 AFR AF: 0.0000522

Gnomad4 AMR AF: 0.0000710

Gnomad4 ASJ AF: 0.000304

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000312

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs542787885; hg19: chr14-29236261;