Genetic Variant FOXP1:c.*3192delA (chr3-70956054-GT-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001349338.3(FOXP1):c.*3192delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 232,760 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

FOXP1
NM_001349338.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.18

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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, ClinGen
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 -9 ACMG points.

BP6

Variant 3-70956054-GT-G is Benign according to our data. Variant chr3-70956054-GT-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 346574.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00105 (160/151914) while in subpopulation NFE AF = 0.00203 (138/67946). AF 95% confidence interval is 0.00175. There are 0 homozygotes in GnomAd4. There are 74 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 160 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FOXP1	NM_001349338.3	MANE Select	c.*3192delA	3_prime_UTR	Exon 21 of 21	NP_001336267.1	Q548T7
FOXP1	NM_001244810.2		c.*3192delA	3_prime_UTR	Exon 21 of 21	NP_001231739.1	Q9H334-8
FOXP1	NM_001244814.3		c.*3192delA	3_prime_UTR	Exon 17 of 17	NP_001231743.1	Q9H334-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.*3192delA		3_prime_UTR	Exon 21 of 21	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.*3192delA		3_prime_UTR	Exon 21 of 21	ENSP00000318902.5	Q9H334-1

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

151796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000664

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00134

AC:

108

AN:

80846

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

AN XY:

37148

show subpopulations

African (AFR)

AF:

0.000257

AC:

AN:

3890

American (AMR)

AF:

0.000401

AC:

AN:

2496

Ashkenazi Jewish (ASJ)

AF:

0.000586

AC:

AN:

5118

East Asian (EAS)

AF:

0.00

AC:

AN:

11374

South Asian (SAS)

AF:

0.00

AC:

AN:

700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.00194

AC:

AN:

49958

Other (OTH)

AF:

0.000888

AC:

AN:

6760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.00105

AC:

160

AN:

151914

Hom.:

Cov.:

AF XY:

0.000996

AC XY:

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41358

American (AMR)

AF:

0.000392

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.000664

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00203

AC:

138

AN:

67946

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000880

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual Disability with Language Impairment and Autistic Features (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over