rs587783634

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BS2BA1BP3

This summary comes from the ClinGen Evidence Repository: The allele frequency of the c.209_235del variant in FOXG1 is 0.17% in Ashkenazi Jewish sub population 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.Gln70_Pro78del variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Gln70_Pro78del variant is an in-frame deletion present in a repetitive region of FOXG1 (BP3). In summary, the p.Gln70_Pro78del variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP3). LINK:https://erepo.genome.network/evrepo/ui/classification/CA172179/MONDO:0100040/033

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel U:1B:5

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP3

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_235delAGCAGCAGCAGCCGCCGCCGCCGCCGC	p.Gln70_Pro78del	disruptive_inframe_deletion	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_235delAGCAGCAGCAGCCGCCGCCGCCGCCGC	p.Gln70_Pro78del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482.1 link	c.209_235delAGCAGCAGCAGCCGCCGCCGCCGCCGC	p.Gln70_Pro78del	disruptive_inframe_deletion	Exon 2 of 2			ENSP00000516406.1
LINC01551	ENST00000675861.1 link	n.374+1475_374+1501delAGCAGCAGCAGCCGCCGCCGCCGCCGC		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.000163

AC:

AN:

128906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000576

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000758

Gnomad ASJ

AF:

0.00130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000200

Gnomad OTH

AF:

0.000565

GnomAD2 exomes

AF:

0.000257

AC:

AN:

73900

AF XY:

0.000258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000299

Gnomad ASJ exome

AF:

0.00157

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

127

AN:

962086

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

467330

show subpopulations

African (AFR)

AF:

0.000256

AC:

AN:

19562

American (AMR)

AF:

0.000213

AC:

AN:

18808

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

13408

East Asian (EAS)

AF:

0.00

AC:

AN:

13832

South Asian (SAS)

AF:

0.0000522

AC:

AN:

38326

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2352

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

804284

Other (OTH)

AF:

0.0000580

AC:

AN:

34458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000163

AC:

AN:

128988

Hom.:

Cov.:

AF XY:

0.0000955

AC XY:

AN XY:

62816

show subpopulations

African (AFR)

AF:

0.0000574

AC:

AN:

34822

American (AMR)

AF:

0.0000757

AC:

AN:

13208

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

3086

East Asian (EAS)

AF:

0.00

AC:

AN:

4266

South Asian (SAS)

AF:

0.00

AC:

AN:

3954

European-Finnish (FIN)

AF:

0.000143

AC:

AN:

6996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.000200

AC:

AN:

59870

Other (OTH)

AF:

0.000559

AC:

AN:

1788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.0000612

Hom.:

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:5

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Rett syndrome, congenital variant

Uncertain:1Benign:1

Oct 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 06, 2014

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jun 21, 2017

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Mar 17, 2017

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

Apr 14, 2023

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 c.209_235del variant in FOXG1 is 0.17% in Ashkenazi Jewish sub population 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.Gln70_Pro78del variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Gln70_Pro78del variant is an in-frame deletion present in a repetitive region of FOXG1 (BP3). In summary, the p.Gln70_Pro78del variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP3).

not provided

Benign:1

Feb 05, 2020

GeneDx

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

=153/47

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