rs794726920

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP5_StrongBS2BA1BP3

This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Q70_P77del variant in FOXG1 is 0.03% in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Q70_P77del variant is observed in at least 2 unaffected individuals (internal database) (BS2). The p.Q70_P77del variant is an in-frame deletion present in a repetitive region of FOXG1 (BP3). The p.Q70_P77del variant is found in at least 3 patients with an alternate molecular basis of disease (internal database) (BP5_strong). In summary, the p.Q70_P77del variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP3, BP5_strong). LINK:https://erepo.genome.network/evrepo/ui/classification/CA238814/MONDO:0100040/016

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel B:6

Conservation

PhyloP100: 2.38

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

For more information check the summary or visit ClinGen Evidence Repository.

BP5

For more information check the summary or visit ClinGen Evidence Repository.

BS2

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5 link	c.209_232delAGCAGCAGCAGCCGCCGCCGCCGC	p.Gln70_Pro77del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000313071.7	NP_005240.3	P55316

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXG1	ENST00000313071.7 link	c.209_232delAGCAGCAGCAGCCGCCGCCGCCGC	p.Gln70_Pro77del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3	P55316
FOXG1	ENST00000706482.1 link	c.209_232delAGCAGCAGCAGCCGCCGCCGCCGC	p.Gln70_Pro77del	disruptive_inframe_deletion	Exon 2 of 2			ENSP00000516406.1	P55316
LINC01551	ENST00000675861.1 link	n.374+1475_374+1498delAGCAGCAGCAGCCGCCGCCGCCGC		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.000186

AC:

AN:

145534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000682

Gnomad ASJ

AF:

0.00533

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000610

Gnomad OTH

AF:

0.000499

GnomAD2 exomes

AF:

0.000412

AC:

AN:

72812

AF XY:

0.000381

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00381

Gnomad EAS exome

AF:

0.000413

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.000488

GnomAD4 exome

AF:

0.000136

AC:

130

AN:

957120

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

463428

show subpopulations

African (AFR)

AF:

0.0000519

AC:

AN:

19284

American (AMR)

AF:

0.00

AC:

AN:

18346

Ashkenazi Jewish (ASJ)

AF:

0.00610

AC:

AN:

13114

East Asian (EAS)

AF:

0.0000773

AC:

AN:

12942

South Asian (SAS)

AF:

0.0000536

AC:

AN:

37290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15564

Middle Eastern (MID)

AF:

0.000429

AC:

AN:

2330

European-Non Finnish (NFE)

AF:

0.0000398

AC:

AN:

804204

Other (OTH)

AF:

0.000382

AC:

AN:

34046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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:

0.000186

AC:

AN:

145534

Hom.:

Cov.:

AF XY:

0.0000707

AC XY:

AN XY:

70698

show subpopulations

African (AFR)

AF:

0.0000494

AC:

AN:

40502

American (AMR)

AF:

0.0000682

AC:

AN:

14666

Ashkenazi Jewish (ASJ)

AF:

0.00533

AC:

AN:

3374

East Asian (EAS)

AF:

0.00

AC:

AN:

5052

South Asian (SAS)

AF:

0.000212

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:

0.0000610

AC:

AN:

65576

Other (OTH)

AF:

0.000499

AC:

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000169

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:1

May 27, 2015

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Aug 28, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

FOXG1 disorder

Benign:1

Mar 26, 2021

ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

The allele frequency of the p.Q70_P77del variant in FOXG1 is 0.03% in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Q70_P77del variant is observed in at least 2 unaffected individuals (internal database) (BS2). The p.Q70_P77del variant is an in-frame deletion present in a repetitive region of FOXG1 (BP3). The p.Q70_P77del variant is found in at least 3 patients with an alternate molecular basis of disease (internal database) (BP5_strong). In summary, the p.Q70_P77del variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP3, BP5_strong). -

not provided

Benign:1

Dec 16, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

FOXG1-related disorder

Benign:1

Sep 27, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Rett syndrome, congenital variant

Benign:1

Jun 28, 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

2.4

Mutation Taster

=158/42

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