chr3-70956489-G-GT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 52 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXP1NM_001349338.3 linkuse as main transcriptc.*2757_*2758insA 3_prime_UTR_variant 21/21 ENST00000649528.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXP1ENST00000649528.3 linkuse as main transcriptc.*2757_*2758insA 3_prime_UTR_variant 21/21 NM_001349338.3 P4Q9H334-1
FOXP1ENST00000318789.11 linkuse as main transcriptc.*2757_*2758insA 3_prime_UTR_variant 21/211 P4Q9H334-1

Frequencies

GnomAD3 genomes
AF:
0.000365
AC:
52
AN:
142632
Hom.:
0
Cov.:
29
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

Intellectual Disability with Language Impairment and Autistic Features Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886058836; hg19: chr3-71005640; API