7-114204894-T-C

Variant names:

• chr7-114204894-T-C
• rs1852638
• ENST00000440349.5:n.-102+41806T>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+41806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 148,874 control chromosomes in the GnomAD database, including 26,837 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 0.57 (26837 hom., cov: 28)
• Consequence: FOXP2 ENST00000703616.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.739 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.286-83125T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000440349.5	TSL:1	n.-102+41806T>C		intron	N/A	ENSP00000395552.1	F8WDL6
	FOXP2	ENST00000703616.1		c.-102+41806T>C		intron	N/A	ENSP00000515400.1	A0A994J6W1
	FOXP2	ENST00000960356.1		c.-102+41806T>C		intron	N/A	ENSP00000630415.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 84707 AN: 148764 Hom.: 26826 Cov.: 28

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.569 AC: 84726 AN: 148874 Hom.: 26837 Cov.: 28 AF XY: 0.575 AC XY: 41704 AN XY: 72576

African (AFR) AF: 0.256 AC: 10110 AN: 39472

American (AMR) AF: 0.751 AC: 11320 AN: 15080

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2655 AN: 3464

East Asian (EAS) AF: 0.605 AC: 3088 AN: 5106

South Asian (SAS) AF: 0.677 AC: 3214 AN: 4744

European-Finnish (FIN) AF: 0.674 AC: 6795 AN: 10082

Middle Eastern (MID) AF: 0.747 AC: 215 AN: 288

European-Non Finnish (NFE) AF: 0.672 AC: 45448 AN: 67664

Other (OTH) AF: 0.608 AC: 1259 AN: 2070

Alfa AF: 0.572 Hom.: 4933

Bravo AF: 0.555

Asia WGS AF: 0.616 AC: 2140 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.43
PhyloP100		-0.36
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: rs1852638; hg19: chr7-113844949;