6-41559960-G-C

Position:

• chr6-41559960-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012426.2(FOXP4):​c.-16-5785G>C 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 152,012 control chromosomes in the GnomAD database, including 9,898 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 (9898 hom., cov: 33)
• Consequence: FOXP4 NM_001012426.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP4	NM_001012426.2	c.-16-5785G>C		intron_variant		ENST00000307972.10	NP_001012426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP4	ENST00000307972.10	c.-16-5785G>C		intron_variant		1	NM_001012426.2	ENSP00000309823	P4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53058 AN: 151894 Hom.: 9864 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.334

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: 53146 AN: 152012 Hom.: 9898 Cov.: 33 AF XY: 0.352 AC XY: 26163 AN XY: 74290

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.340

Alfa AF: 0.325 Hom.: 1031

Bravo AF: 0.357

Asia WGS AF: 0.354 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs9381080; hg19: chr6-41527698;