dbSNP rs112803404: FOXG1:p.Ala149Ala (chr14-28767726-C-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005249.5(FOXG1):c.447C>G(p.Ala149Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000792 in 1,514,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A149A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.189

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: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 14-28767726-C-G is Benign according to our data. Variant chr14-28767726-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1214020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.189 with no splicing effect.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5 link	c.447C>G	p.Ala149Ala	synonymous_variant	Exon 1 of 1	ENST00000313071.7	NP_005240.3	P55316

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXG1	ENST00000313071.7 link	c.447C>G	p.Ala149Ala	synonymous_variant	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3	P55316
FOXG1	ENST00000706482.1 link	c.447C>G	p.Ala149Ala	synonymous_variant	Exon 2 of 2			ENSP00000516406.1	P55316
LINC01551	ENST00000675861.1 link	n.374+1713C>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

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

GnomAD2 exomes

AF:

0.0000153

AC:

AN:

131114

AF XY:

0.0000279

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000201

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000733

AC:

AN:

1364848

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

672992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31368

American (AMR)

AF:

0.0000562

AC:

AN:

35612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24818

East Asian (EAS)

AF:

0.00

AC:

AN:

35664

South Asian (SAS)

AF:

0.00

AC:

AN:

78590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4024

European-Non Finnish (NFE)

AF:

0.00000752

AC:

AN:

1064270

Other (OTH)

AF:

0.00

AC:

AN:

57058

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:

0.0000134

AC:

AN:

149696

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

73020

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40876

American (AMR)

AF:

0.000133

AC:

AN:

15042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

5012

South Asian (SAS)

AF:

0.00

AC:

AN:

4644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67214

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 03, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Rett syndrome, congenital variant

Benign:1

Jan 19, 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

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

-0.19

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over