Genetic Variant FOXP4:c.-211C>G (chr6-41546673-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001012426.2(FOXP4):c.-211C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 147,118 control chromosomes in the GnomAD database, including 11,612 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 0.38 ( 11602 hom., cov: 31)

Exomes 𝑓: 0.40 ( 10 hom. )

Consequence

FOXP4
NM_001012426.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0400

Publications

9 publications found

Variant links:

Genes affected

FOXP4 (HGNC:20842): (forkhead box P4) 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. Many members of the forkhead box gene family, including members of subfamily P, have roles in mammalian oncogenesis. This gene may play a role in the development of tumors of the kidney and larynx. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms. [provided by RefSeq, Jul 2008]

FOXP4 links:

FOXP4-AS1 (HGNC:50332): (FOXP4 antisense RNA 1)

FOXP4-AS1 links:

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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=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP4	NM_001012426.2 link	c.-211C>G		5_prime_UTR_variant	Exon 1 of 17	ENST00000307972.10	NP_001012426.1	Q8IVH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP4	ENST00000307972.10 link	c.-211C>G		5_prime_UTR_variant	Exon 1 of 17	1	NM_001012426.2	ENSP00000309823.4		Q8IVH2-1

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

55808

AN:

146894

Hom.:

11562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.551

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.397

AC:

AN:

116

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.444

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.265

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.380

AC:

55898

AN:

147002

Hom.:

11602

Cov.:

AF XY:

0.384

AC XY:

27489

AN XY:

71582

show subpopulations

African (AFR)

AF:

0.552

AC:

22629

AN:

41002

American (AMR)

AF:

0.392

AC:

5805

AN:

14822

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

869

AN:

3388

East Asian (EAS)

AF:

0.344

AC:

1743

AN:

5062

South Asian (SAS)

AF:

0.337

AC:

1623

AN:

4814

European-Finnish (FIN)

AF:

0.366

AC:

3170

AN:

8670

Middle Eastern (MID)

AF:

0.252

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.286

AC:

18879

AN:

65996

Other (OTH)

AF:

0.364

AC:

746

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1692

3385

5077

6770

8462

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:

0.345

Hom.:

1196

Asia WGS

AF:

0.316

AC:

810

AN:

2566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

-0.040

PromoterAI

-0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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