rs717233

Variant names:

• chr7-114213034-T-C
• rs717233
• ENST00000440349.5:n.-102+49946T>C

Variant summary

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

The ENST00000703616.1(FOXP2):​c.-102+49946T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,162 control chromosomes in the GnomAD database, including 5,273 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 0.25 (5273 hom., cov: 32)
• Consequence: FOXP2 ENST00000703616.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 4 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000703616.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	NR_033766.2		n.286-74985T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000440349.5	TSL:1	n.-102+49946T>C		intron	N/A	ENSP00000395552.1
	FOXP2	ENST00000703616.1		c.-102+49946T>C		intron	N/A	ENSP00000515400.1
	FOXP2	ENST00000960356.1		c.-102+49946T>C		intron	N/A	ENSP00000630415.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37661 AN: 152044 Hom.: 5259 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0344

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.248 AC: 37713 AN: 152162 Hom.: 5273 Cov.: 32 AF XY: 0.241 AC XY: 17935 AN XY: 74398

African (AFR) AF: 0.338 AC: 14035 AN: 41486

American (AMR) AF: 0.161 AC: 2454 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3472

East Asian (EAS) AF: 0.0339 AC: 176 AN: 5186

South Asian (SAS) AF: 0.0748 AC: 361 AN: 4828

European-Finnish (FIN) AF: 0.243 AC: 2574 AN: 10582

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.249 AC: 16954 AN: 68006

Other (OTH) AF: 0.229 AC: 484 AN: 2114

Alfa AF: 0.240 Hom.: 13796

Bravo AF: 0.247

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.60
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs717233; hg19: chr7-113853089;