chr3-70955830-G-GCACACACA

Variant names:

• chr3-70955830-G-GCACACACA
• rs886058826
• NM_001349338.3:c.*3416_*3417insTGTGTGTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001349338.3(FOXP1):​c.*3416_*3417insTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 205,668 control chromosomes in the GnomAD database, including 14 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0042 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0089 (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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 535 AN: 126512 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.000905

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000592

Gnomad ASJ AF: 0.000300

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.000621

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000182

Gnomad OTH AF: 0.00447

GnomAD4 exome AF: 0.00890 AC: 704 AN: 79102 Hom.: 0 Cov.: 0 AF XY: 0.00906 AC XY: 330 AN XY: 36438

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

African (AFR) AF: 0.000870 AC: 3 AN: 3448

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

Ashkenazi Jewish (ASJ) AF: 0.000795 AC: 4 AN: 5032

East Asian (EAS) AF: 0.0627 AC: 654 AN: 10426

South Asian (SAS) AF: 0.00130 AC: 1 AN: 772

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

Middle Eastern (MID) AF: 0.00207 AC: 1 AN: 484

European-Non Finnish (NFE) AF: 0.000141 AC: 7 AN: 49544

Other (OTH) AF: 0.00514 AC: 34 AN: 6614

⚠️ 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: 0.00420 AC: 531 AN: 126566 Hom.: 14 Cov.: 32 AF XY: 0.00494 AC XY: 305 AN XY: 61702

African (AFR) AF: 0.000902 AC: 21 AN: 23278

American (AMR) AF: 0.000591 AC: 8 AN: 13526

Ashkenazi Jewish (ASJ) AF: 0.000300 AC: 1 AN: 3334

East Asian (EAS) AF: 0.124 AC: 455 AN: 3676

South Asian (SAS) AF: 0.00476 AC: 20 AN: 4200

European-Finnish (FIN) AF: 0.000621 AC: 6 AN: 9664

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

European-Non Finnish (NFE) AF: 0.000182 AC: 12 AN: 65910

Other (OTH) AF: 0.00444 AC: 8 AN: 1802

Alfa AF: 0.000217 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism

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;