Genetic Variant FOXG1:c.-210delT (chr14-28767055-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005249.5(FOXG1):c.-210delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 143,078 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 18 hom., cov: 29)

Exomes 𝑓: 0.068 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0490

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 -10 ACMG points.

BP6

Variant 14-28767055-CT-C is Benign according to our data. Variant chr14-28767055-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1188300.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5 link	c.-210delT		5_prime_UTR_variant	Exon 1 of 1	ENST00000313071.7	NP_005240.3	P55316

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	ENST00000313071 link	c.-210delT	5_prime_UTR_variant	Exon 1 of 1	NM_005249.5	ENSP00000339004.3	P55316
FOXG1	ENST00000706482 link	c.-210delT	5_prime_UTR_variant	Exon 2 of 2		ENSP00000516406.1	P55316
LINC01551	ENST00000675861.1 link	n.374+1057delT	intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1524

AN:

139646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00626

Gnomad ASJ

AF:

0.000304

Gnomad EAS

AF:

0.00165

Gnomad SAS

AF:

0.000905

Gnomad FIN

AF:

0.000130

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.0685

AC:

235

AN:

3432

Hom.:

Cov.:

AF XY:

0.0759

AC XY:

149

AN XY:

1962

show subpopulations

Gnomad4 AFR exome

AF:

0.0400

AC:

AN:

Gnomad4 AMR exome

AF:

0.200

AC:

AN:

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

Gnomad4 EAS exome

AF:

0.0357

AC:

AN:

Gnomad4 SAS exome

AF:

0.119

AC:

AN:

464

Gnomad4 FIN exome

AF:

0.0459

AC:

AN:

196

Gnomad4 NFE exome

AF:

0.0626

AC:

158

AN:

2522

Gnomad4 Remaining exome

AF:

0.0385

AC:

AN:

104

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.0109

AC:

1522

AN:

139646

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

726

AN XY:

67582

show subpopulations

Gnomad4 AFR

AF:

0.0337

AC:

0.0337058

AN:

0.0337058

Gnomad4 AMR

AF:

0.00625

AC:

0.00625

AN:

0.00625

Gnomad4 ASJ

AF:

0.000304

AC:

0.000303951

AN:

0.000303951

Gnomad4 EAS

AF:

0.00165

AC:

0.00165426

AN:

0.00165426

Gnomad4 SAS

AF:

0.000911

AC:

0.000911162

AN:

0.000911162

Gnomad4 FIN

AF:

0.000130

AC:

0.000129534

AN:

0.000129534

Gnomad4 NFE

AF:

0.00170

AC:

0.00170366

AN:

0.00170366

Gnomad4 OTH

AF:

0.0105

AC:

0.0104822

AN:

0.0104822

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 21, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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

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