dbSNP rs786200975: FOXG1:p.Pro77_Pro79del (chr14-28767497-AGCCGCCGCC-A) – 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.228_236delGCCGCCGCC(p.Pro77_Pro79del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000613 in 978,372 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.51

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: Likely_benign. The variant received -3 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005249.5

BP6

Variant 14-28767497-AGCCGCCGCC-A is Benign according to our data. Variant chr14-28767497-AGCCGCCGCC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1094650.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.228_236delGCCGCCGCC	p.Pro77_Pro79del	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.228_236delGCCGCCGCC	p.Pro77_Pro79del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482.1 link	c.228_236delGCCGCCGCC	p.Pro77_Pro79del	disruptive_inframe_deletion	Exon 2 of 2			ENSP00000516406.1
LINC01551	ENST00000675861.1 link	n.374+1494_374+1502delGCCGCCGCC		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000214

AC:

AN:

139878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000777

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

AF:

0.00000358

AC:

AN:

838494

Hom.:

AF XY:

0.00000251

AC XY:

AN XY:

398112

show subpopulations

African (AFR)

AF:

0.000192

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:

0.00

AC:

AN:

748524

Other (OTH)

AF:

0.00

AC:

AN:

28798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000214

AC:

AN:

139878

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

68002

show subpopulations

African (AFR)

AF:

0.0000777

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:

0.00

AC:

AN:

63692

Other (OTH)

AF:

0.00

AC:

AN:

1898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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.:

Bravo

AF:

0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Rett syndrome, congenital variant

Benign:1

Jul 31, 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

2.5

Mutation Taster

=180/20

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