14-28767530-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_005249.5(FOXG1):c.251C>G(p.Pro84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 147,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P84H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Consequence

FOXG1
NM_005249.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.467

Publications

0 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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08721593).

BP6

Variant 14-28767530-C-G is Benign according to our data. Variant chr14-28767530-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 281382.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005249.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	NM_005249.5	MANE Select	c.251C>G	p.Pro84Arg	missense	Exon 1 of 1	NP_005240.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FOXG1	ENST00000313071.7	TSL:6 MANE Select	c.251C>G	p.Pro84Arg	missense	Exon 1 of 1	ENSP00000339004.3
FOXG1	ENST00000706482.1		c.251C>G	p.Pro84Arg	missense	Exon 2 of 2	ENSP00000516406.1
LINC01551	ENST00000675861.1		n.374+1517C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

147192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000675

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

Cov.:

GnomAD4 genome

AF:

0.0000136

AC:

AN:

147192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71600

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40826

American (AMR)

AF:

0.0000675

AC:

AN:

14804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66222

Other (OTH)

AF:

0.00

AC:

AN:

2026

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Rett syndrome, congenital variant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.49

M_CAP

Benign

0.040

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

0.47

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.060

REVEL

Benign

0.022

Sift

Uncertain

0.0070

Sift4G

Benign

0.41

Polyphen

0.028

Vest4

0.12

MutPred

0.28

Gain of catalytic residue at P79 (P = 0.0047)

MVP

0.19

ClinPred

0.20

GERP RS

2.0

Varity_R

0.10

gMVP

0.19

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over