Genetic Variant FOXG1:p.His53_His54dup (chr14-28767417-G-GCACCAC) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3BP6_Moderate

The NM_005249.5(FOXG1):c.156_161dupCCACCA(p.His53_His54dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000433 in 1,385,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. H54H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.512

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 -3 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005249.5

BP6

Variant 14-28767417-G-GCACCAC is Benign according to our data. Variant chr14-28767417-G-GCACCAC is described in ClinVar as Likely_benign. ClinVar VariationId is 1085933.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5 link	c.156_161dupCCACCA	p.His53_His54dup	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.156_161dupCCACCA	p.His53_His54dup	disruptive_inframe_insertion	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482.1 link	c.156_161dupCCACCA	p.His53_His54dup	disruptive_inframe_insertion	Exon 2 of 2			ENSP00000516406.1
LINC01551	ENST00000675861.1 link	n.374+1422_374+1427dupCCACCA		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000140

AC:

AN:

143126

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:

0.000220

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000154

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000143

AC:

AN:

139964

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000271

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000322

AC:

AN:

1242518

Hom.:

Cov.:

AF XY:

0.00000325

AC XY:

AN XY:

615220

show subpopulations

African (AFR)

AF:

0.0000394

AC:

AN:

25398

American (AMR)

AF:

0.00

AC:

AN:

30694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19030

East Asian (EAS)

AF:

0.00

AC:

AN:

24694

South Asian (SAS)

AF:

0.00

AC:

AN:

72994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40782

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4008

European-Non Finnish (NFE)

AF:

0.00000204

AC:

AN:

978040

Other (OTH)

AF:

0.0000213

AC:

AN:

46878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

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:

0.0000140

AC:

AN:

143126

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

69430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39358

American (AMR)

AF:

0.00

AC:

AN:

14508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3340

East Asian (EAS)

AF:

0.00

AC:

AN:

4890

South Asian (SAS)

AF:

0.000220

AC:

AN:

4542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

65052

Other (OTH)

AF:

0.00

AC:

AN:

1936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Rett syndrome, congenital variant

Benign:1

Mar 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.51

Mutation Taster

=79/21

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over