rs17508329
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The ENST00000440349.5(FOXP2):c.-246-3834A>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 152,250 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.011 ( 8 hom., cov: 32)
Consequence
FOXP2
ENST00000440349.5 intron, NMD_transcript
ENST00000440349.5 intron, NMD_transcript
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.32
Genes affected
FOXP2 (HGNC:13875): (forkhead box P2) This gene encodes a member of the forkhead/winged-helix (FOX) family of transcription factors. It is expressed in fetal and adult brain as well as in several other organs such as the lung and gut. The protein product contains a FOX DNA-binding domain and a large polyglutamine tract and is an evolutionarily conserved transcription factor, which may bind directly to approximately 300 to 400 gene promoters in the human genome to regulate the expression of a variety of genes. This gene is required for proper development of speech and language regions of the brain during embryogenesis, and may be involved in a variety of biological pathways and cascades that may ultimately influence language development. Mutations in this gene cause speech-language disorder 1 (SPCH1), also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Multiple alternative transcripts encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1728/152250) while in subpopulation NFE AF= 0.0169 (1150/68000). AF 95% confidence interval is 0.0161. There are 8 homozygotes in gnomad4. There are 829 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1728 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXP2 | NR_033766.2 | n.285+72499A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXP2 | ENST00000440349.5 | c.-246-3834A>C | intron_variant, NMD_transcript_variant | 1 | |||||
FOXP2 | ENST00000635638.1 | c.-246-3834A>C | intron_variant | 5 | |||||
FOXP2 | ENST00000703612.1 | c.-246-3834A>C | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0114 AC: 1728AN: 152132Hom.: 8 Cov.: 32
GnomAD3 genomes
?
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32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0113 AC: 1728AN: 152250Hom.: 8 Cov.: 32 AF XY: 0.0111 AC XY: 829AN XY: 74438
GnomAD4 genome
?
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1728
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152250
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32
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829
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74438
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6
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at