14-28768762-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_005249.5(FOXG1):c.*13C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.017 in 1,613,930 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 15 hom., cov: 32)

Exomes 𝑓: 0.017 ( 248 hom. )

Consequence

FOXG1
NM_005249.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.58

Publications

3 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 14-28768762-C-A is Benign according to our data. Variant chr14-28768762-C-A is described in ClinVar as Benign. ClinVar VariationId is 95263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0128 (1944/152174) while in subpopulation AMR AF = 0.0251 (383/15280). AF 95% confidence interval is 0.023. There are 15 homozygotes in GnomAd4. There are 949 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1944 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5 link	c.*13C>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000313071.7	NP_005240.3	P55316

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXG1	ENST00000313071.7 link	c.*13C>A	3_prime_UTR_variant	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3	P55316
FOXG1	ENST00000706482.1 link	c.*13C>A	3_prime_UTR_variant	Exon 2 of 2			ENSP00000516406.1	P55316
LINC01551	ENST00000675861.1 link	n.374+2749C>A	intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1944

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00353

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0252

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0101

GnomAD2 exomes

AF:

0.0164

AC:

4120

AN:

251124

AF XY:

0.0152

show subpopulations

Gnomad AFR exome

AF:

0.00324

Gnomad AMR exome

AF:

0.0421

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0174

AC:

25436

AN:

1461756

Hom.:

248

Cov.:

AF XY:

0.0169

AC XY:

12312

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.00257

AC:

AN:

33478

American (AMR)

AF:

0.0388

AC:

1734

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00210

AC:

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.00544

AC:

469

AN:

86242

European-Finnish (FIN)

AF:

0.0123

AC:

657

AN:

53414

Middle Eastern (MID)

AF:

0.00416

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0193

AC:

21505

AN:

1111912

Other (OTH)

AF:

0.0149

AC:

899

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

1309

2617

3926

5234

6543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.0128

AC:

1944

AN:

152174

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

949

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00352

AC:

146

AN:

41526

American (AMR)

AF:

0.0251

AC:

383

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.000580

AC:

AN:

5172

South Asian (SAS)

AF:

0.00477

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0118

AC:

125

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0181

AC:

1234

AN:

68012

Other (OTH)

AF:

0.00997

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

196

295

393

491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0146

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 17, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 04, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

3.6

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over