rs6935737

Variant names:

• chr6-41546673-C-G
• rs6935737
• NM_001012426.2:c.-211C>G

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP4	NM_001012426.2	MANE Select	c.-211C>G		5_prime_UTR	Exon 1 of 17	NP_001012426.1	Q8IVH2-1
	FOXP4	NM_001012427.2		c.-211C>G		5_prime_UTR	Exon 1 of 17	NP_001012427.1	Q8IVH2-2
	FOXP4	NM_001405824.1		c.-211C>G		5_prime_UTR	Exon 1 of 17	NP_001392753.1	B7ZBM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP4	ENST00000307972.10	TSL:1 MANE Select	c.-211C>G		5_prime_UTR	Exon 1 of 17	ENSP00000309823.4	Q8IVH2-1
	FOXP4	ENST00000373057.7	TSL:1	c.-211C>G		5_prime_UTR	Exon 1 of 17	ENSP00000362148.3	Q8IVH2-2
	FOXP4	ENST00000373063.7	TSL:1	c.-211C>G		5_prime_UTR	Exon 1 of 17	ENSP00000362154.3	Q8IVH2-3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.444 AC: 32 AN: 72

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.265 AC: 9 AN: 34

Other (OTH) AF: 0.667 AC: 4 AN: 6

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

African (AFR) AF: 0.552 AC: 22629 AN: 41002

American (AMR) AF: 0.392 AC: 5805 AN: 14822

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 869 AN: 3388

East Asian (EAS) AF: 0.344 AC: 1743 AN: 5062

South Asian (SAS) AF: 0.337 AC: 1623 AN: 4814

European-Finnish (FIN) AF: 0.366 AC: 3170 AN: 8670

Middle Eastern (MID) AF: 0.252 AC: 73 AN: 290

European-Non Finnish (NFE) AF: 0.286 AC: 18879 AN: 65996

Other (OTH) AF: 0.364 AC: 746 AN: 2052

Alfa AF: 0.345 Hom.: 1196

Asia WGS AF: 0.316 AC: 810 AN: 2566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		-0.040
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6935737; hg19: chr6-41514411;