3-70956415-CTTT-C

Variant names:

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

Variant summary

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

The NM_001349338.3(FOXP1):​c.*2829_*2831delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 184,710 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 0.00014 (0 hom., cov: 26)
  • Exomes 𝑓: 0.015 (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.*2829_*2831delAAA		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_*2831delAAA		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789.11	c.*2829_*2831delAAA		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.000143 AC: 18 AN: 125902 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000790

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000244

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000724

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000101

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0153 AC: 898 AN: 58802 Hom.: 0 AF XY: 0.0159 AC XY: 431 AN XY: 27188

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

African (AFR) AF: 0.0147 AC: 40 AN: 2724

American (AMR) AF: 0.0188 AC: 33 AN: 1754

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 46 AN: 3660

East Asian (EAS) AF: 0.0114 AC: 103 AN: 9000

South Asian (SAS) AF: 0.0143 AC: 7 AN: 490

European-Finnish (FIN) AF: 0.00267 AC: 1 AN: 374

Middle Eastern (MID) AF: 0.0296 AC: 11 AN: 372

European-Non Finnish (NFE) AF: 0.0163 AC: 579 AN: 35546

Other (OTH) AF: 0.0160 AC: 78 AN: 4882

⚠️ 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: 0.000143 AC: 18 AN: 125908 Hom.: 0 Cov.: 26 AF XY: 0.000182 AC XY: 11 AN XY: 60518

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

African (AFR) AF: 0.000151 AC: 5 AN: 33144

American (AMR) AF: 0.0000789 AC: 1 AN: 12676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3130

East Asian (EAS) AF: 0.000245 AC: 1 AN: 4088

South Asian (SAS) AF: 0.00 AC: 0 AN: 3852

European-Finnish (FIN) AF: 0.000724 AC: 5 AN: 6904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.000101 AC: 6 AN: 59380

Other (OTH) AF: 0.00 AC: 0 AN: 1684

⚠️ 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;