3-70955830-G-GCACACACACACACACA

Variant names:

• chr3-70955830-G-GCACACACACACACACA
• rs886058826
• NM_001349338.3:c.*3416_*3417insTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001349338.3(FOXP1):​c.*3416_*3417insTGTGTGTGTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 126,580 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000016 (0 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000158 (2/126580) while in subpopulation EAS AF = 0.000543 (2/3686). AF 95% confidence interval is 0.0000957. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.*3416_*3417insTGTGTGTGTGTGTGTG		3_prime_UTR	Exon 21 of 21	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.*3416_*3417insTGTGTGTGTGTGTGTG		3_prime_UTR	Exon 21 of 21	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244814.3		c.*3416_*3417insTGTGTGTGTGTGTGTG		3_prime_UTR	Exon 17 of 17	NP_001231743.1	Q9H334-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.*3416_*3417insTGTGTGTGTGTGTGTG		3_prime_UTR	Exon 21 of 21	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.*3416_*3417insTGTGTGTGTGTGTGTG		3_prime_UTR	Exon 21 of 21	ENSP00000318902.5	Q9H334-1

Frequencies

GnomAD3 genomes AF: 0.0000158 AC: 2 AN: 126526 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000541

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000158 AC: 2 AN: 126580 Hom.: 0 Cov.: 32 AF XY: 0.0000162 AC XY: 1 AN XY: 61714

African (AFR) AF: 0.00 AC: 0 AN: 23278

American (AMR) AF: 0.00 AC: 0 AN: 13526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3334

East Asian (EAS) AF: 0.000543 AC: 2 AN: 3686

South Asian (SAS) AF: 0.00 AC: 0 AN: 4200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65912

Other (OTH) AF: 0.00 AC: 0 AN: 1804

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886058826; hg19: chr3-71004981;