Genetic Variant FOXP1:c.*3676delA (chr3-70955570-GT-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001349338.3(FOXP1):c.*3676delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 214,288 control chromosomes in the GnomAD database, including 103 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 102 hom., cov: 30)

Exomes 𝑓: 0.022 ( 1 hom. )

Consequence

FOXP1
NM_001349338.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.620

Publications

1 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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3 link	c.*3676delA		3_prime_UTR_variant	Exon 21 of 21	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3 link	c.*3676delA		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1		Q9H334-1
FOXP1	ENST00000318789.11 link	c.*3676delA		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5		Q9H334-1

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3096

AN:

144600

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0707

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00931

Gnomad ASJ

AF:

0.000299

Gnomad EAS

AF:

0.00159

Gnomad SAS

AF:

0.00109

Gnomad FIN

AF:

0.00168

Gnomad MID

AF:

0.00338

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.0152

GnomAD4 exome

AF:

0.0218

AC:

1520

AN:

69636

Hom.:

Cov.:

AF XY:

0.0209

AC XY:

670

AN XY:

32056

show subpopulations

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

African (AFR)

AF:

0.0789

AC:

275

AN:

3486

American (AMR)

AF:

0.0250

AC:

AN:

2124

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

4330

East Asian (EAS)

AF:

0.00425

AC:

AN:

10588

South Asian (SAS)

AF:

0.0127

AC:

AN:

628

European-Finnish (FIN)

AF:

0.0174

AC:

AN:

172

Middle Eastern (MID)

AF:

0.0244

AC:

AN:

450

European-Non Finnish (NFE)

AF:

0.0208

AC:

876

AN:

42090

Other (OTH)

AF:

0.0274

AC:

158

AN:

5768

⚠️ 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: 0.292

Heterozygous variant carriers

164

328

493

657

821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0214

AC:

3101

AN:

144652

Hom.:

102

Cov.:

AF XY:

0.0215

AC XY:

1513

AN XY:

70344

show subpopulations

African (AFR)

AF:

0.0706

AC:

2828

AN:

40040

American (AMR)

AF:

0.00930

AC:

134

AN:

14408

Ashkenazi Jewish (ASJ)

AF:

0.000299

AC:

AN:

3348

East Asian (EAS)

AF:

0.00159

AC:

AN:

5028

South Asian (SAS)

AF:

0.00110

AC:

AN:

4564

European-Finnish (FIN)

AF:

0.00168

AC:

AN:

8910

Middle Eastern (MID)

AF:

0.00368

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.00121

AC:

AN:

65204

Other (OTH)

AF:

0.0151

AC:

AN:

1990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

141

282

422

563

704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000724

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.62

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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3-70955570-GTTTT-GTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over