7-114658653-C-T

Variant names:

• chr7-114658653-C-T
• rs17213159
• NM_014491.4:c.1468+386C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014491.4(FOXP2):​c.1468+386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 152,216 control chromosomes in the GnomAD database, including 686 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 0.081 (686 hom., cov: 32)
• Consequence: FOXP2 NM_014491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 8 publications found

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]

FOXP2 Gene-Disease associations (from GenCC):

• specific language disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• childhood apraxia of speech

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000303050 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP2	NM_014491.4	c.1468+386C>T		intron_variant	Intron 11 of 16	ENST00000350908.9	NP_055306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000350908.9	c.1468+386C>T		intron_variant	Intron 11 of 16	1	NM_014491.4	ENSP00000265436.7

Frequencies

GnomAD3 genomes AF: 0.0815 AC: 12395 AN: 152098 Hom.: 686 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0814 AC: 12387 AN: 152216 Hom.: 686 Cov.: 32 AF XY: 0.0800 AC XY: 5956 AN XY: 74426

African (AFR) AF: 0.0210 AC: 871 AN: 41550

American (AMR) AF: 0.0919 AC: 1404 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0265 AC: 128 AN: 4824

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8053 AN: 68004

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.103 Hom.: 2128

Bravo AF: 0.0772

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17213159; hg19: chr7-114298708;