rs13093086

Variant names:

• chr3-71006011-G-A
• rs13093086
• NM_001349338.3:c.975-4952C>T

Variant summary

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

The NM_001349338.3(FOXP1):​c.975-4952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,896 control chromosomes in the GnomAD database, including 12,886 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 0.37 (12886 hom., cov: 31)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 11 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, ClinGen
• 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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	NM_001349338.3	MANE Select	c.975-4952C>T		intron	N/A	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.975-4952C>T		intron	N/A	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244814.3		c.975-4952C>T		intron	N/A	NP_001231743.1	Q9H334-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.975-4952C>T		intron	N/A	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.975-4952C>T		intron	N/A	ENSP00000318902.5	Q9H334-1
	ENSG00000285708	ENST00000647725.1		c.975-4952C>T		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55532 AN: 151776 Hom.: 12885 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.366 AC: 55527 AN: 151896 Hom.: 12886 Cov.: 31 AF XY: 0.358 AC XY: 26578 AN XY: 74230

African (AFR) AF: 0.115 AC: 4761 AN: 41458

American (AMR) AF: 0.496 AC: 7553 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1819 AN: 3468

East Asian (EAS) AF: 0.0217 AC: 112 AN: 5164

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4822

European-Finnish (FIN) AF: 0.436 AC: 4588 AN: 10532

Middle Eastern (MID) AF: 0.472 AC: 137 AN: 290

European-Non Finnish (NFE) AF: 0.503 AC: 34148 AN: 67916

Other (OTH) AF: 0.390 AC: 823 AN: 2108

Alfa AF: 0.436 Hom.: 12174

Bravo AF: 0.359

Asia WGS AF: 0.128 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		1.9
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: rs13093086; hg19: chr3-71055162;