3-70955832-GCACACACACACA-GCACACA

Variant names:

• chr3-70955832-GCACACA-G
• rs143202281
• NM_001349338.3:c.*3409_*3414delTGTGTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001349338.3(FOXP1):​c.*3409_*3414delTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 221,612 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 0.00041 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00071 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 3 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.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000407 (60/147260) while in subpopulation EAS AF = 0.00299 (15/5016). AF 95% confidence interval is 0.00184. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3409_*3414delTGTGTG		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.*3409_*3414delTGTGTG		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789.11	c.*3409_*3414delTGTGTG		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 60 AN: 147164 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000819

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000683

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00298

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000136

Gnomad OTH AF: 0.000494

GnomAD4 exome AF: 0.000713 AC: 53 AN: 74352 Hom.: 0 AF XY: 0.000849 AC XY: 29 AN XY: 34148

African (AFR) AF: 0.000262 AC: 1 AN: 3810

American (AMR) AF: 0.00 AC: 0 AN: 2290

Ashkenazi Jewish (ASJ) AF: 0.000215 AC: 1 AN: 4644

East Asian (EAS) AF: 0.00353 AC: 39 AN: 11050

South Asian (SAS) AF: 0.00 AC: 0 AN: 712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 446

European-Non Finnish (NFE) AF: 0.000245 AC: 11 AN: 44944

Other (OTH) AF: 0.000163 AC: 1 AN: 6140

GnomAD4 genome AF: 0.000407 AC: 60 AN: 147260 Hom.: 0 Cov.: 26 AF XY: 0.000517 AC XY: 37 AN XY: 71616

African (AFR) AF: 0.000817 AC: 33 AN: 40408

American (AMR) AF: 0.0000683 AC: 1 AN: 14652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00299 AC: 15 AN: 5016

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000136 AC: 9 AN: 66364

Other (OTH) AF: 0.000489 AC: 1 AN: 2046

Alfa AF: 0.00 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs143202281; hg19: chr3-71004983;