Variant 6-41565857-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001012426.2(FOXP4):c.97G>A(p.Gly33Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00395 in 1,613,894 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 19 hom. )

Consequence

FOXP4
NM_001012426.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.18

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00581941).

BP6

Variant 6-41565857-G-A is Benign according to our data. Variant chr6-41565857-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024777.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP4	NM_001012426.2 linkuse as main transcript	c.97G>A	p.Gly33Arg	missense_variant	2/17	ENST00000307972.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP4	ENST00000307972.10 linkuse as main transcript	c.97G>A	p.Gly33Arg	missense_variant	2/17	1	NM_001012426.2	P4	Q8IVH2-1

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

433

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00313

AC:

782

AN:

250130

Hom.:

AF XY:

0.00325

AC XY:

441

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.000798

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00550

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00406

AC:

5938

AN:

1461602

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

2848

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.00363

Gnomad4 NFE exome

AF:

0.00485

Gnomad4 OTH exome

AF:

0.00263

GnomAD4 genome

AF:

0.00284

AC:

433

AN:

152292

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000867

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.00501

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00438

Hom.:

Bravo

AF:

0.00236

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00582

AC:

ExAC

AF:

0.00357

AC:

433

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00463

EpiControl

AF:

0.00379

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

FOXP4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;.;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

T;T;T;T;.

M_CAP

Benign

0.081

MetaRNN

Benign

0.0058

T;T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.90

L;L;.;L;L

MutationTaster

Benign

0.88

N;N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.13

N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.38

T;T;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T

Polyphen

0.027

B;.;.;.;B

Vest4

0.14

MutPred

0.27

Gain of methylation at G33 (P = 0.0121);Gain of methylation at G33 (P = 0.0121);Gain of methylation at G33 (P = 0.0121);Gain of methylation at G33 (P = 0.0121);Gain of methylation at G33 (P = 0.0121);

MVP

0.50

MPC

0.11

ClinPred

0.021

GERP RS

5.0

Varity_R

0.034

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over