3-70956415-CTTTTTTT-CTTT

Variant names:

• chr3-70956415-CTTTT-C
• rs112098084
• NM_001349338.3:c.*2828_*2831delAAAA

Variant summary

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

The NM_001349338.3(FOXP1):​c.*2828_*2831delAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 185,966 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.000040 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0038 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• 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.*2828_*2831delAAAA		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.*2828_*2831delAAAA		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789.11	c.*2828_*2831delAAAA		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.0000397 AC: 5 AN: 125934 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000258

Gnomad FIN AF: 0.000145

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000337

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00378 AC: 227 AN: 60032 Hom.: 0 AF XY: 0.00371 AC XY: 103 AN XY: 27752

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

African (AFR) AF: 0.00396 AC: 11 AN: 2778

American (AMR) AF: 0.00393 AC: 7 AN: 1782

Ashkenazi Jewish (ASJ) AF: 0.00270 AC: 10 AN: 3698

East Asian (EAS) AF: 0.00272 AC: 25 AN: 9176

South Asian (SAS) AF: 0.00202 AC: 1 AN: 496

European-Finnish (FIN) AF: 0.00532 AC: 2 AN: 376

Middle Eastern (MID) AF: 0.00811 AC: 3 AN: 370

European-Non Finnish (NFE) AF: 0.00413 AC: 150 AN: 36344

Other (OTH) AF: 0.00359 AC: 18 AN: 5012

⚠️ 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: 0.0000397 AC: 5 AN: 125934 Hom.: 0 Cov.: 26 AF XY: 0.0000496 AC XY: 3 AN XY: 60508

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

African (AFR) AF: 0.0000302 AC: 1 AN: 33098

American (AMR) AF: 0.00 AC: 0 AN: 12660

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

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

South Asian (SAS) AF: 0.000258 AC: 1 AN: 3880

European-Finnish (FIN) AF: 0.000145 AC: 1 AN: 6914

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

European-Non Finnish (NFE) AF: 0.0000337 AC: 2 AN: 59406

Other (OTH) AF: 0.00 AC: 0 AN: 1672

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 45

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs112098084; hg19: chr3-71005566;