rs12674004

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014491.4(FOXP2):​c.258+2090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 151,354 control chromosomes in the GnomAD database, including 1,223 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 0.088 ( 1223 hom., cov: 32)

Consequence

FOXP2
NM_014491.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0540
Variant links:
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=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXP2NM_014491.4 linkuse as main transcriptc.258+2090G>A intron_variant ENST00000350908.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXP2ENST00000350908.9 linkuse as main transcriptc.258+2090G>A intron_variant 1 NM_014491.4 P1O15409-1

Frequencies

GnomAD3 genomes
AF:
0.0878
AC:
13277
AN:
151238
Hom.:
1216
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.230
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0639
Gnomad ASJ
AF:
0.0533
Gnomad EAS
AF:
0.154
Gnomad SAS
AF:
0.118
Gnomad FIN
AF:
0.0158
Gnomad MID
AF:
0.0570
Gnomad NFE
AF:
0.0138
Gnomad OTH
AF:
0.0704
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0880
AC:
13312
AN:
151354
Hom.:
1223
Cov.:
32
AF XY:
0.0881
AC XY:
6516
AN XY:
73974
show subpopulations
Gnomad4 AFR
AF:
0.231
Gnomad4 AMR
AF:
0.0640
Gnomad4 ASJ
AF:
0.0533
Gnomad4 EAS
AF:
0.154
Gnomad4 SAS
AF:
0.118
Gnomad4 FIN
AF:
0.0158
Gnomad4 NFE
AF:
0.0138
Gnomad4 OTH
AF:
0.0711
Alfa
AF:
0.0548
Hom.:
89
Bravo
AF:
0.0999
Asia WGS
AF:
0.135
AC:
467
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.0
DANN
Benign
0.45

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: rs12674004; hg19: chr7-114176851; API