Genetic Variant FOXG1:c.-211_-210dupTT (chr14-28767055-C-CTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490

Publications

0 publications found

Variant links:

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]

FOXG1 links:

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

LINC01551 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005249.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	NM_005249.5	MANE Select	c.-211_-210dupTT		5_prime_UTR	Exon 1 of 1	NP_005240.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FOXG1	ENST00000313071.7	TSL:6 MANE Select	c.-211_-210dupTT	5_prime_UTR	Exon 1 of 1	ENSP00000339004.3	P55316
FOXG1	ENST00000706482.1		c.-211_-210dupTT	5_prime_UTR	Exon 2 of 2	ENSP00000516406.1	P55316
LINC01551	ENST00000675861.1		n.374+1056_374+1057dupTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000501

AC:

AN:

139686

Hom.:

Cov.:

show subpopulations

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:

AN:

3448

Hom.:

Cov.:

AF XY:

0.00355

AC XY:

AN XY:

1974

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00214

AC:

AN:

468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00276

AC:

AN:

2532

Other (OTH)

AF:

0.00

AC:

AN:

106

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000230926), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.300

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000573

AC:

AN:

139686

Hom.:

Cov.:

AF XY:

0.0000444

AC XY:

AN XY:

67606

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000522

AC:

AN:

38314

American (AMR)

AF:

0.0000710

AC:

AN:

14080

Ashkenazi Jewish (ASJ)

AF:

0.000304

AC:

AN:

3290

East Asian (EAS)

AF:

0.00

AC:

AN:

4836

South Asian (SAS)

AF:

0.00

AC:

AN:

4390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7720

Middle Eastern (MID)

AF:

0.00769

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0000312

AC:

AN:

64008

Other (OTH)

AF:

0.00

AC:

AN:

1908

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000467366), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.382

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.049

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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14-28767055-CTTTTTTT-CTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over