rs886058826

Variant names:

• chr3-70955830-G-GCA
• rs886058826
• NM_001349338.3:c.*3416_*3417insTG

Your query was ambiguous. Multiple possible variants found:

• chr3-70955830-G-GCA
• chr3-70955830-G-GCACA
• chr3-70955830-G-GCACACA
• chr3-70955830-G-GCACACACA
• chr3-70955830-G-GCACACACACA
• chr3-70955830-G-GCACACACACACA
• chr3-70955830-G-GCACACACACACACA
• chr3-70955830-G-GCACACACACACACACA
• chr3-70955830-G-GCACGCACACA
• chr3-70955830-G-GCACGCACACACA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001349338.3(FOXP1):​c.*3416_*3417insTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 205,752 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• 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: 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3416_*3417insTG		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.*3416_*3417insTG		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789.11	c.*3416_*3417insTG		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

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

Gnomad AFR AF: 0.0000431

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000238

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000379 AC: 3 AN: 79226 Hom.: 0 Cov.: 0 AF XY: 0.0000274 AC XY: 1 AN XY: 36496

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

African (AFR) AF: 0.00 AC: 0 AN: 3450

American (AMR) AF: 0.00 AC: 0 AN: 2412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5032

East Asian (EAS) AF: 0.000190 AC: 2 AN: 10540

South Asian (SAS) AF: 0.00 AC: 0 AN: 772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 486

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49546

Other (OTH) AF: 0.000151 AC: 1 AN: 6618

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000005), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000158 AC: 2 AN: 126526 Hom.: 0 Cov.: 32 AF XY: 0.0000162 AC XY: 1 AN XY: 61638

African (AFR) AF: 0.0000431 AC: 1 AN: 23214

American (AMR) AF: 0.00 AC: 0 AN: 13504

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3696

South Asian (SAS) AF: 0.000238 AC: 1 AN: 4206

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65920

Other (OTH) AF: 0.00 AC: 0 AN: 1790

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;