3-70956415-C-CTTT

Variant names:

• chr3-70956415-C-CTTT
• rs112098084
• NM_001349338.3:c.*2829_*2831dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001349338.3(FOXP1):​c.*2829_*2831dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000059 in 186,580 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961
• 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: Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*2829_*2831dupAAA		3_prime_UTR_variant	Exon 21 of 21	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.*2829_*2831dupAAA		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789.11	c.*2829_*2831dupAAA		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.0000159 AC: 2 AN: 125948 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000790

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000168

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000148 AC: 9 AN: 60632 Hom.: 0 Cov.: 0 AF XY: 0.000107 AC XY: 3 AN XY: 28048

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000357 AC: 1 AN: 2804

American (AMR) AF: 0.00 AC: 0 AN: 1806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3742

East Asian (EAS) AF: 0.000108 AC: 1 AN: 9286

South Asian (SAS) AF: 0.00 AC: 0 AN: 508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 380

European-Non Finnish (NFE) AF: 0.000164 AC: 6 AN: 36658

Other (OTH) AF: 0.000197 AC: 1 AN: 5070

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000159 AC: 2 AN: 125948 Hom.: 0 Cov.: 26 AF XY: 0.0000330 AC XY: 2 AN XY: 60516

African (AFR) AF: 0.00 AC: 0 AN: 33100

American (AMR) AF: 0.0000790 AC: 1 AN: 12662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3132

East Asian (EAS) AF: 0.00 AC: 0 AN: 4098

South Asian (SAS) AF: 0.00 AC: 0 AN: 3880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.0000168 AC: 1 AN: 59414

Other (OTH) AF: 0.00 AC: 0 AN: 1670

Alfa AF: 0.00 Hom.: 45

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.96

Splicing

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

Other links and lift over

dbSNP: rs112098084; hg19: chr3-71005566;