3-70956489-G-GT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001349338.3(FOXP1):c.*2757_*2758insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 207,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0087 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000364 (52/142722) while in subpopulation AFR AF= 0.000846 (33/39010). AF 95% confidence interval is 0.000619. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd at 52 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP1	NM_001349338.3	c.*2757_*2758insA		3_prime_UTR_variant	21/21	ENST00000649528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP1	ENST00000649528.3	c.*2757_*2758insA		3_prime_UTR_variant	21/21		NM_001349338.3	P4
FOXP1	ENST00000318789.11	c.*2757_*2758insA		3_prime_UTR_variant	21/21	1		P4

Frequencies

GnomAD3 genomes AF: 0.000365 AC: 52 AN: 142632 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000848

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000353

Gnomad ASJ AF: 0.000596

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000670

Gnomad FIN AF: 0.000116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000123

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00869 AC: 560 AN: 64468 Hom.: 0 Cov.: 0 AF XY: 0.00802 AC XY: 238 AN XY: 29674

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.00718

Gnomad4 EAS exome AF: 0.00554

Gnomad4 SAS exome AF: 0.00929

Gnomad4 FIN exome AF: 0.00427

Gnomad4 NFE exome AF: 0.00924

Gnomad4 OTH exome AF: 0.00833

GnomAD4 genome AF: 0.000364 AC: 52 AN: 142722 Hom.: 0 Cov.: 29 AF XY: 0.000404 AC XY: 28 AN XY: 69298

Gnomad4 AFR AF: 0.000846

Gnomad4 AMR AF: 0.000352

Gnomad4 ASJ AF: 0.000596

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000672

Gnomad4 FIN AF: 0.000116

Gnomad4 NFE AF: 0.000123

Gnomad4 OTH AF: 0.00

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual Disability with Language Impairment and Autistic Features Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs886058836; hg19: chr3-71005640;