Variant 14-28767417-GCACCAC-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.156_161delCCACCA(p.His53_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 0.0000426 in 1,385,244 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: 30)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.89

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-GCACCAC-G is Benign according to our data. Variant chr14-28767417-GCACCAC-G is described in ClinVar as [Likely_benign]. Clinvar id is 569855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAdExome4 at 56 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXG1	NM_005249.5 linkuse as main transcript	c.156_161delCCACCA	p.His53_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.156_161delCCACCA	p.His53_His54del	disruptive_inframe_deletion	1/1	6	NM_005249.5	ENSP00000339004.3	P55316
FOXG1	ENST00000706482.1 linkuse as main transcript	c.156_161delCCACCA	p.His53_His54del	disruptive_inframe_deletion	2/2			ENSP00000516406.1	P55316
LINC01551	ENST00000675861.1 linkuse as main transcript	n.374+1422_374+1427delCCACCA		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0000210

AC:

AN:

143126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000762

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

GnomAD3 exomes

AF:

0.0000500

AC:

AN:

139964

Hom.:

AF XY:

0.0000392

AC XY:

AN XY:

76586

show subpopulations

Gnomad AFR exome

AF:

0.000162

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000136

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000173

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000451

AC:

AN:

1242118

Hom.:

AF XY:

0.0000504

AC XY:

AN XY:

615016

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000228

Gnomad4 ASJ exome

AF:

0.000105

Gnomad4 EAS exome

AF:

0.000122

Gnomad4 SAS exome

AF:

0.0000822

Gnomad4 FIN exome

AF:

0.0000491

Gnomad4 NFE exome

AF:

0.0000327

Gnomad4 OTH exome

AF:

0.0000640

GnomAD4 genome

AF:

0.0000210

AC:

AN:

143126

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

69430

show subpopulations

Gnomad4 AFR

AF:

0.0000762

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2017

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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

FOXG1: BP3 -

Rett syndrome, congenital variant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

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