Genetic Variant NM_001349338.3:c.-168+12231G>A (chr3-71481195-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001349338.3(FOXP1):c.-168+12231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,050 control chromosomes in the GnomAD database, including 10,440 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10440 hom., cov: 32)

Consequence

FOXP1
NM_001349338.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113

Publications

21 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:

ENSG00000285708 (HGNC:):

ENSG00000285708 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3 link	c.-168+12231G>A		intron_variant	Intron 3 of 20	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3 link	c.-168+12231G>A		intron_variant	Intron 3 of 20		NM_001349338.3	ENSP00000497369.1		Q9H334-1
ENSG00000285708	ENST00000647725.1 link	c.-290+12231G>A		intron_variant	Intron 7 of 25			ENSP00000497585.1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55027

AN:

151932

Hom.:

10429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.404

Gnomad EAS

AF:

0.00597

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.366

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.362

AC:

55061

AN:

152050

Hom.:

10440

Cov.:

AF XY:

0.357

AC XY:

26530

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.397

AC:

16467

AN:

41448

American (AMR)

AF:

0.294

AC:

4495

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

1403

AN:

3472

East Asian (EAS)

AF:

0.00598

AC:

AN:

5182

South Asian (SAS)

AF:

0.280

AC:

1348

AN:

4822

European-Finnish (FIN)

AF:

0.388

AC:

4095

AN:

10558

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26015

AN:

67974

Other (OTH)

AF:

0.361

AC:

762

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1792

3585

5377

7170

8962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.348

Hom.:

5598

Bravo

AF:

0.352

Asia WGS

AF:

0.153

AC:

534

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.0

(source)

DANN

Benign

0.54

PhyloP100

-0.11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over