Genetic Variant FOXP1:c.*2473_*2482delTAAAAAAAAA (chr3-70956764-TTTTTTTTTTA-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001349338.3(FOXP1):c.*2473_*2482delTAAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 0)

Exomes 𝑓: 0.000062 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXP1
NM_001349338.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.504

Publications

0 publications found

Variant links:

Genes affected

FOXP1 (HGNC:3823): (forkhead box P1) This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FOXP1 Gene-Disease associations (from GenCC):

intellectual disability-severe speech delay-mild dysmorphism syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

FOXP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3 link	c.2473_2482delTAAAAAAAAA		3_prime_UTR_variant	Exon 21 of 21	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXP1	ENST00000649528.3 link	c.2473_2482delTAAAAAAAAA	3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1	Q9H334-1
FOXP1	ENST00000318789.11 link	c.2473_2482delTAAAAAAAAA	3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5	Q9H334-1
FOXP1	ENST00000615603.5 link	n.4938_4947delTAAAAAAAAA	non_coding_transcript_exon_variant	Exon 20 of 20	5

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

303

AN:

126882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000900

Gnomad AMI

AF:

0.0140

Gnomad AMR

AF:

0.000729

Gnomad ASJ

AF:

0.00122

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000513

Gnomad FIN

AF:

0.000260

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00391

Gnomad OTH

AF:

0.00236

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000624

AC:

AN:

64130

Hom.:

AF XY:

0.0000330

AC XY:

AN XY:

30294

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000411

AC:

AN:

2432

American (AMR)

AF:

0.00

AC:

AN:

1802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4004

East Asian (EAS)

AF:

0.00

AC:

AN:

9348

South Asian (SAS)

AF:

0.00

AC:

AN:

590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

394

European-Non Finnish (NFE)

AF:

0.0000751

AC:

AN:

39966

Other (OTH)

AF:

0.00

AC:

AN:

5152

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00239

AC:

303

AN:

126958

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

115

AN XY:

61288

show subpopulations

African (AFR)

AF:

0.000897

AC:

AN:

30102

American (AMR)

AF:

0.000727

AC:

AN:

12372

Ashkenazi Jewish (ASJ)

AF:

0.00122

AC:

AN:

3266

East Asian (EAS)

AF:

0.00

AC:

AN:

4604

South Asian (SAS)

AF:

0.000515

AC:

AN:

3884

European-Finnish (FIN)

AF:

0.000260

AC:

AN:

7700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00391

AC:

243

AN:

62188

Other (OTH)

AF:

0.00233

AC:

AN:

1716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00135

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual Disability with Language Impairment and Autistic Features

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.50

Splicing

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

Publications

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chr3-70956764-TTTTTTTTTTA-T

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