7-114386035-G-C

Variant names:

• chr7-114386035-G-C
• rs2894697
• ENST00000440349.5:n.-10-40467G>C

Variant summary

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

The ENST00000440349.5(FOXP2):​n.-10-40467G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,240 control chromosomes in the GnomAD database, including 16,132 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 0.43 (16132 hom., cov: 33)
• Consequence: FOXP2 ENST00000440349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000440349.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	NR_033766.2		n.377-40467G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000440349.5	TSL:1	n.-10-40467G>C		intron	N/A	ENSP00000395552.1
	FOXP2	ENST00000703616.1		c.-10-40467G>C		intron	N/A	ENSP00000515400.1
	FOXP2	ENST00000703613.1		c.-10-40467G>C		intron	N/A	ENSP00000515397.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65453 AN: 152122 Hom.: 16135 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.430 AC: 65452 AN: 152240 Hom.: 16132 Cov.: 33 AF XY: 0.434 AC XY: 32335 AN XY: 74424

African (AFR) AF: 0.175 AC: 7268 AN: 41542

American (AMR) AF: 0.431 AC: 6600 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3472

East Asian (EAS) AF: 0.625 AC: 3219 AN: 5150

South Asian (SAS) AF: 0.555 AC: 2678 AN: 4828

European-Finnish (FIN) AF: 0.542 AC: 5752 AN: 10608

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36094 AN: 68018

Other (OTH) AF: 0.473 AC: 1000 AN: 2116

Alfa AF: 0.502 Hom.: 681

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.46
PhyloP100		-1.5
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: rs2894697; hg19: chr7-114026090;