6-41559960-G-C

Variant names:

• chr6-41559960-G-C
• rs9381080
• NM_001012426.2:c.-16-5785G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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-AS1 (HGNC:50332): (FOXP4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOXP4	NM_001012426.2	c.-16-5785G>C		intron_variant	Intron 1 of 16	ENST00000307972.10	NP_001012426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP4	ENST00000307972.10	c.-16-5785G>C		intron_variant	Intron 1 of 16	1	NM_001012426.2	ENSP00000309823.4

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

African (AFR) AF: 0.476 AC: 19701 AN: 41428

American (AMR) AF: 0.375 AC: 5733 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1796 AN: 5180

South Asian (SAS) AF: 0.333 AC: 1601 AN: 4812

European-Finnish (FIN) AF: 0.330 AC: 3483 AN: 10558

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

European-Non Finnish (NFE) AF: 0.277 AC: 18827 AN: 67986

Other (OTH) AF: 0.340 AC: 715 AN: 2104

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
PhyloP100		-1.3
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: rs9381080; hg19: chr6-41527698;