rs6935737

Positions:

• chr6-41546673-C-G

Variant summary

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

The NM_001012426.2(FOXP4):​c.-211C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 147,118 control chromosomes in the GnomAD database, including 11,612 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 0.38 (11602 hom., cov: 31)
  • Exomes 𝑓: 0.40 (10 hom.)
• Consequence: FOXP4 NM_001012426.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP4	NM_001012426.2	c.-211C>G		5_prime_UTR_variant	1/17	ENST00000307972.10
FOXP4-AS1	NR_126415.1	n.244+1705G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP4	ENST00000307972.10	c.-211C>G		5_prime_UTR_variant	1/17	1	NM_001012426.2	P4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 55808 AN: 146894 Hom.: 11562 Cov.: 31

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.397 AC: 46 AN: 116 Hom.: 10 Cov.: 0 AF XY: 0.333 AC XY: 22 AN XY: 66

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.444

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.380 AC: 55898 AN: 147002 Hom.: 11602 Cov.: 31 AF XY: 0.384 AC XY: 27489 AN XY: 71582

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.364

Alfa AF: 0.345 Hom.: 1196

Asia WGS AF: 0.316 AC: 810 AN: 2566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs6935737; hg19: chr6-41514411;