chr7-114101050-T-G

Variant names:

• chr7-114101050-T-G
• rs6466479
• ENST00000440349.5:n.-247+14439T>G

Variant summary

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

The ENST00000440349.5(FOXP2):​n.-247+14439T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,888 control chromosomes in the GnomAD database, including 7,932 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 0.26 (7932 hom., cov: 32)
• Consequence: FOXP2 ENST00000440349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP2	NR_033766.2	n.285+14439T>G		intron_variant	Intron 1 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000440349.5	n.-247+14439T>G		intron_variant	Intron 1 of 11	1		ENSP00000395552.1
FOXP2	ENST00000703616.1	c.-247+13212T>G		intron_variant	Intron 1 of 20			ENSP00000515400.1
FOXP2	ENST00000703613.1	c.-365+14439T>G		intron_variant	Intron 1 of 20			ENSP00000515397.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39309 AN: 151770 Hom.: 7908 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.259 AC: 39390 AN: 151888 Hom.: 7932 Cov.: 32 AF XY: 0.262 AC XY: 19464 AN XY: 74208

African (AFR) AF: 0.548 AC: 22686 AN: 41392

American (AMR) AF: 0.200 AC: 3042 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3464

East Asian (EAS) AF: 0.493 AC: 2526 AN: 5126

South Asian (SAS) AF: 0.258 AC: 1241 AN: 4812

European-Finnish (FIN) AF: 0.115 AC: 1220 AN: 10578

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7590 AN: 67958

Other (OTH) AF: 0.237 AC: 499 AN: 2106

Alfa AF: 0.252 Hom.: 4405

Bravo AF: 0.278

Asia WGS AF: 0.356 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.15
DANN	Benign	0.52
PhyloP100		-2.1
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: rs6466479; hg19: chr7-113741105;