Genetic Variant FOXG1:p.Gln70_Pro77dup (chr14-28767473-C-CGCCGCCGCCGCCGCAGCAGCAGCA) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_005249.5(FOXG1):c.209_232dupAGCAGCAGCAGCCGCCGCCGCCGC(p.Gln70_Pro77dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 145,534 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P78P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXG1
NM_005249.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.718

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: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005249.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5 link	c.209_232dupAGCAGCAGCAGCCGCCGCCGCCGC	p.Gln70_Pro77dup	disruptive_inframe_insertion	Exon 1 of 1	ENST00000313071.7	NP_005240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FOXG1	ENST00000313071.7 link	c.209_232dupAGCAGCAGCAGCCGCCGCCGCCGC	p.Gln70_Pro77dup	disruptive_inframe_insertion	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482.1 link	c.209_232dupAGCAGCAGCAGCCGCCGCCGCCGC	p.Gln70_Pro77dup	disruptive_inframe_insertion	Exon 2 of 2			ENSP00000516406.1
LINC01551	ENST00000675861.1 link	n.374+1475_374+1498dupAGCAGCAGCAGCCGCCGCCGCCGC		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000687

AC:

AN:

145534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000247

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000104

AC:

AN:

957124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

463430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19284

American (AMR)

AF:

0.00

AC:

AN:

18346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13116

East Asian (EAS)

AF:

0.00

AC:

AN:

12942

South Asian (SAS)

AF:

0.00

AC:

AN:

37290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2330

European-Non Finnish (NFE)

AF:

0.00000124

AC:

AN:

804206

Other (OTH)

AF:

0.00

AC:

AN:

34046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.875

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:

0.00000687

AC:

AN:

145534

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70698

show subpopulations

African (AFR)

AF:

0.0000247

AC:

AN:

40502

American (AMR)

AF:

0.00

AC:

AN:

14666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3374

East Asian (EAS)

AF:

0.00

AC:

AN:

5052

South Asian (SAS)

AF:

0.00

AC:

AN:

4722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65576

Other (OTH)

AF:

0.00

AC:

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.72

Mutation Taster

=88/12

polymorphism

(source)

Splicing

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

Publications

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14-28767473-CGCCGCCGCCGCCGCAGCAGCAGCA-CGCCGCCGCCGCCGCAGCAGCAGCAGCCGCCGCCGCCGCAGCAGCAGCA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over