Variant chr14-28767417-GCACCACCAC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_005249.5(FOXG1):c.153_161delCCACCACCA(p.His52_His54del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,385,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel B:4

Conservation

PhyloP100: 2.54

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:):

LINC01551 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 14-28767417-GCACCACCAC-G is Benign according to our data. Variant chr14-28767417-GCACCACCAC-G is described in ClinVar as [Benign]. Clinvar id is 205462.Status of the report is reviewed_by_expert_panel, 3 stars.

BS2

High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXG1	NM_005249.5 linkuse as main transcript	c.153_161delCCACCACCA	p.His52_His54del	disruptive_inframe_deletion	1/1	ENST00000313071.7	NP_005240.3	P55316

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FOXG1	ENST00000313071.7 linkuse as main transcript	c.153_161delCCACCACCA	p.His52_His54del	disruptive_inframe_deletion	1/1	6	NM_005249.5	ENSP00000339004.3	P55316
FOXG1	ENST00000706482.1 linkuse as main transcript	c.153_161delCCACCACCA	p.His52_His54del	disruptive_inframe_deletion	2/2			ENSP00000516406.1	P55316
LINC01551	ENST00000675861.1 linkuse as main transcript	n.374+1419_374+1427delCCACCACCA		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0000279

AC:

AN:

143126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000254

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:

0.0000461

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000143

AC:

AN:

139964

Hom.:

AF XY:

0.0000131

AC XY:

AN XY:

76586

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000480

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000173

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1242496

Hom.:

AF XY:

0.0000195

AC XY:

AN XY:

615206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000394

Gnomad4 AMR exome

AF:

0.0000326

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000137

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000279

AC:

AN:

143126

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69430

show subpopulations

Gnomad4 AFR

AF:

0.0000254

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000461

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 27, 2014

The variant is found in EPILEPSY panel(s). -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2018

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

Benign, reviewed by expert panel

curation

ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel

Jun 25, 2024

The highest population minor allele frequency of the c.153_161del (p.His55_His57del) variant in FOXG1 in gnomAD v4.1 is 0.00023 in the Middle Eastern population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.00008) for BS1, and therefore meets this criterion (BS1). The p.His55_His57del variant is observed in at least 2 unaffected individuals (Internal database - Invitae, Internal database - GeneDx) (BS2). The p.His55_His57del variant is an in-frame deletion present in a repetitive region of FOXG1 (BP3). In summary, the p.His55_His57del variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP3). -

Rett syndrome, congenital variant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over