Genetic Variant FOXG1:c.-13dupC (chr14-28767261-T-TC) – 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.-13dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000787 in 1,144,170 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), 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 0.0 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXG1
NM_005249.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.326

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.-13dupC		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.-13dupC	5_prime_UTR	Exon 1 of 1	ENSP00000339004.3	P55316
FOXG1	ENST00000706482.1		c.-13dupC	5_prime_UTR	Exon 2 of 2	ENSP00000516406.1	P55316
LINC01551	ENST00000675861.1		n.374+1254dupC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

128114

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

124866

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000787

AC:

AN:

1144170

Hom.:

Cov.:

AF XY:

0.00000886

AC XY:

AN XY:

564428

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:

22156

American (AMR)

AF:

0.00

AC:

AN:

24658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15244

East Asian (EAS)

AF:

0.00

AC:

AN:

14784

South Asian (SAS)

AF:

0.0000294

AC:

AN:

67914

European-Finnish (FIN)

AF:

0.0000572

AC:

AN:

34968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4288

European-Non Finnish (NFE)

AF:

0.00000544

AC:

AN:

919270

Other (OTH)

AF:

0.00

AC:

AN:

40888

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000739231), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

128114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62218

African (AFR)

AF:

0.00

AC:

AN:

34150

American (AMR)

AF:

0.00

AC:

AN:

12792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3166

East Asian (EAS)

AF:

0.00

AC:

AN:

4290

South Asian (SAS)

AF:

0.00

AC:

AN:

3996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60348

Other (OTH)

AF:

0.00

AC:

AN:

1754

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.33

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

14-28767261-TC-TCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over