6-41576055-C-A

Variant names:

• chr6-41576055-C-A
• rs6458228
• NM_001012426.2:c.205-1931C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012426.2(FOXP4):​c.205-1931C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 150,188 control chromosomes in the GnomAD database, including 10,021 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 0.35 (10021 hom., cov: 26)
• Consequence: FOXP4 NM_001012426.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP4	NM_001012426.2	c.205-1931C>A		intron_variant	Intron 2 of 16	ENST00000307972.10	NP_001012426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP4	ENST00000307972.10	c.205-1931C>A		intron_variant	Intron 2 of 16	1	NM_001012426.2	ENSP00000309823.4

Frequencies

GnomAD3 genomes AF: 0.351 AC: 52651 AN: 150080 Hom.: 9987 Cov.: 26

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.216

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.351 AC: 52734 AN: 150188 Hom.: 10021 Cov.: 26 AF XY: 0.354 AC XY: 25920 AN XY: 73272

African (AFR) AF: 0.477 AC: 19568 AN: 40988

American (AMR) AF: 0.377 AC: 5702 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 863 AN: 3436

East Asian (EAS) AF: 0.342 AC: 1725 AN: 5048

South Asian (SAS) AF: 0.336 AC: 1592 AN: 4742

European-Finnish (FIN) AF: 0.330 AC: 3420 AN: 10366

Middle Eastern (MID) AF: 0.222 AC: 64 AN: 288

European-Non Finnish (NFE) AF: 0.279 AC: 18769 AN: 67250

Other (OTH) AF: 0.341 AC: 701 AN: 2054

Alfa AF: 0.173 Hom.: 333

Bravo AF: 0.357

Asia WGS AF: 0.356 AC: 1238 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.37
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6458228; hg19: chr6-41543793;