chr6-41568689-C-T

Variant names:

• chr6-41568689-C-T
• rs1983891
• NM_001012426.2:c.204+2725C>T

Variant summary

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

The NM_001012426.2(FOXP4):​c.204+2725C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,036 control chromosomes in the GnomAD database, including 9,900 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 (9900 hom., cov: 32)
• Consequence: FOXP4 NM_001012426.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 84 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP4	NM_001012426.2	c.204+2725C>T		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.204+2725C>T		intron_variant	Intron 2 of 16	1	NM_001012426.2	ENSP00000309823.4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53079 AN: 151918 Hom.: 9867 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.350 AC: 53164 AN: 152036 Hom.: 9900 Cov.: 32 AF XY: 0.352 AC XY: 26184 AN XY: 74316

African (AFR) AF: 0.477 AC: 19758 AN: 41446

American (AMR) AF: 0.377 AC: 5756 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1756 AN: 5146

South Asian (SAS) AF: 0.332 AC: 1596 AN: 4810

European-Finnish (FIN) AF: 0.330 AC: 3488 AN: 10574

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18831 AN: 67990

Other (OTH) AF: 0.338 AC: 714 AN: 2110

Alfa AF: 0.291 Hom.: 26052

Bravo AF: 0.357

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		-0.26
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: rs1983891; hg19: chr6-41536427;