NM_001349338.3:c.-297-30429A>C

Variant names:

• chr3-71523984-T-G
• rs17008723
• NM_001349338.3:c.-297-30429A>C

Variant summary

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

The NM_001349338.3(FOXP1):​c.-297-30429A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,032 control chromosomes in the GnomAD database, including 1,842 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 0.15 (1842 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 5 publications found

Genes affected

FOXP1 (HGNC:3823): (forkhead box P1) 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. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FOXP1 Gene-Disease associations (from GenCC):

• intellectual disability-severe speech delay-mild dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000285708 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	NM_001349338.3	MANE Select	c.-297-30429A>C		intron	N/A	NP_001336267.1
	FOXP1	NM_001244810.2		c.-297-30429A>C		intron	N/A	NP_001231739.1
	FOXP1	NM_001244816.2		c.-298+19440A>C		intron	N/A	NP_001231745.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.-297-30429A>C		intron	N/A	ENSP00000497369.1
	FOXP1	ENST00000318789.11	TSL:1	c.-297-30429A>C		intron	N/A	ENSP00000318902.5
	ENSG00000285708	ENST00000647725.1		c.-419-30429A>C		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22146 AN: 151914 Hom.: 1839 Cov.: 32

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.146 AC: 22160 AN: 152032 Hom.: 1842 Cov.: 32 AF XY: 0.145 AC XY: 10796 AN XY: 74310

African (AFR) AF: 0.0906 AC: 3756 AN: 41454

American (AMR) AF: 0.141 AC: 2161 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.0589 AC: 305 AN: 5178

South Asian (SAS) AF: 0.135 AC: 649 AN: 4814

European-Finnish (FIN) AF: 0.165 AC: 1739 AN: 10554

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12450 AN: 67976

Other (OTH) AF: 0.154 AC: 324 AN: 2104

Alfa AF: 0.172 Hom.: 2918

Bravo AF: 0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.74
PhyloP100		-0.080
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: rs17008723; hg19: chr3-71573135;