Genetic Variant FOXG1:p.Pro77_Pro79dup (chr14-28767497-A-AGCCGCCGCC) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_005249.5(FOXG1):c.228_236dupGCCGCCGCC(p.Pro77_Pro79dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000204 in 978,372 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 0.0000071 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.33

Publications

1 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_005249.5

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	NM_005249.5	MANE Select	c.228_236dupGCCGCCGCC	p.Pro77_Pro79dup	disruptive_inframe_insertion	Exon 1 of 1	NP_005240.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FOXG1	ENST00000313071.7	TSL:6 MANE Select	c.228_236dupGCCGCCGCC	p.Pro77_Pro79dup	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000339004.3
FOXG1	ENST00000706482.1		c.228_236dupGCCGCCGCC	p.Pro77_Pro79dup	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000516406.1
LINC01551	ENST00000675861.1		n.374+1494_374+1502dupGCCGCCGCC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000715

AC:

AN:

139878

Hom.:

Cov.:

show subpopulations

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:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000119

AC:

AN:

838494

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

398112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15642

American (AMR)

AF:

0.00

AC:

AN:

2948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6304

East Asian (EAS)

AF:

0.00

AC:

AN:

8344

South Asian (SAS)

AF:

0.00

AC:

AN:

18110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1824

European-Non Finnish (NFE)

AF:

0.00000134

AC:

AN:

748524

Other (OTH)

AF:

0.00

AC:

AN:

28798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

AF:

0.00000715

AC:

AN:

139878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38588

American (AMR)

AF:

0.00

AC:

AN:

14230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3276

East Asian (EAS)

AF:

0.00

AC:

AN:

4700

South Asian (SAS)

AF:

0.00

AC:

AN:

4428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

252

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

63692

Other (OTH)

AF:

0.00

AC:

AN:

1898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=78/22

polymorphism

(source)

Splicing

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

Publications

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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