chr7-114323279-G-A

Variant names:

• chr7-114323279-G-A
• rs1358278
• ENST00000440349.5:n.-11+35170G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000440349.5(FOXP2):​n.-11+35170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,828 control chromosomes in the GnomAD database, including 16,055 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 0.45 (16055 hom., cov: 32)
• Consequence: FOXP2 ENST00000440349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP2	NR_033766.2	n.376+35170G>A		intron_variant	Intron 2 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000440349.5	n.-11+35170G>A		intron_variant	Intron 3 of 11	1		ENSP00000395552.1
FOXP2	ENST00000703616.1	c.-11+35170G>A		intron_variant	Intron 3 of 20			ENSP00000515400.1
FOXP2	ENST00000703613.1	c.-11+35170G>A		intron_variant	Intron 4 of 20			ENSP00000515397.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68529 AN: 151710 Hom.: 16040 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.452 AC: 68576 AN: 151828 Hom.: 16055 Cov.: 32 AF XY: 0.451 AC XY: 33469 AN XY: 74196

African (AFR) AF: 0.570 AC: 23618 AN: 41412

American (AMR) AF: 0.378 AC: 5773 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 991 AN: 3472

East Asian (EAS) AF: 0.498 AC: 2577 AN: 5172

South Asian (SAS) AF: 0.404 AC: 1945 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4859 AN: 10534

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27532 AN: 67846

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.404 Hom.: 37345

Bravo AF: 0.452

Asia WGS AF: 0.426 AC: 1478 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.60
PhyloP100		1.1
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: rs1358278; hg19: chr7-113963334;