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6-41565841-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001012426.2(FOXP4):c.81C>A(p.Ala27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,613,620 control chromosomes in the GnomAD database, including 71,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 9788 hom., cov: 32)
Exomes 𝑓: 0.29 ( 62144 hom. )

Consequence

FOXP4
NM_001012426.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.78
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-41565841-C-A is Benign according to our data. Variant chr6-41565841-C-A is described in ClinVar as [Benign]. Clinvar id is 1224246.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.78 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXP4NM_001012426.2 linkuse as main transcriptc.81C>A p.Ala27= synonymous_variant 2/17 ENST00000307972.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXP4ENST00000307972.10 linkuse as main transcriptc.81C>A p.Ala27= synonymous_variant 2/171 NM_001012426.2 P4Q8IVH2-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.347
AC:
52753
AN:
151848
Hom.:
9759
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.473
Gnomad AMI
AF:
0.393
Gnomad AMR
AF:
0.375
Gnomad ASJ
AF:
0.247
Gnomad EAS
AF:
0.339
Gnomad SAS
AF:
0.331
Gnomad FIN
AF:
0.329
Gnomad MID
AF:
0.212
Gnomad NFE
AF:
0.275
Gnomad OTH
AF:
0.336
GnomAD3 exomes
AF:
0.319
AC:
79813
AN:
250250
Hom.:
13327
AF XY:
0.310
AC XY:
42064
AN XY:
135500
show subpopulations
Gnomad AFR exome
AF:
0.479
Gnomad AMR exome
AF:
0.410
Gnomad ASJ exome
AF:
0.243
Gnomad EAS exome
AF:
0.335
Gnomad SAS exome
AF:
0.319
Gnomad FIN exome
AF:
0.327
Gnomad NFE exome
AF:
0.272
Gnomad OTH exome
AF:
0.300
GnomAD4 exome
AF:
0.288
AC:
420758
AN:
1461654
Hom.:
62144
Cov.:
37
AF XY:
0.289
AC XY:
209873
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.476
Gnomad4 AMR exome
AF:
0.406
Gnomad4 ASJ exome
AF:
0.245
Gnomad4 EAS exome
AF:
0.366
Gnomad4 SAS exome
AF:
0.322
Gnomad4 FIN exome
AF:
0.325
Gnomad4 NFE exome
AF:
0.271
Gnomad4 OTH exome
AF:
0.300
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.348
AC:
52835
AN:
151966
Hom.:
9788
Cov.:
32
AF XY:
0.350
AC XY:
26008
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.474
Gnomad4 AMR
AF:
0.375
Gnomad4 ASJ
AF:
0.247
Gnomad4 EAS
AF:
0.339
Gnomad4 SAS
AF:
0.331
Gnomad4 FIN
AF:
0.329
Gnomad4 NFE
AF:
0.275
Gnomad4 OTH
AF:
0.338
Alfa
AF:
0.286
Hom.:
12744
Bravo
AF:
0.355
Asia WGS
AF:
0.348
AC:
1212
AN:
3478
EpiCase
AF:
0.258
EpiControl
AF:
0.265

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 22, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
0.16
Dann
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs2104506; hg19: chr6-41533579; COSMIC: COSV57220407; COSMIC: COSV57220407; API