chr7-114374519-T-C

Variant names:

• chr7-114374519-T-C
• rs10249531
• ENST00000440349.5:n.-10-51983T>C

Variant summary

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

The ENST00000703616.1(FOXP2):​c.-10-51983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,028 control chromosomes in the GnomAD database, including 10,548 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 0.36 (10548 hom., cov: 32)
• Consequence: FOXP2 ENST00000703616.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	NR_033766.2		n.377-51983T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000440349.5	TSL:1	n.-10-51983T>C		intron	N/A	ENSP00000395552.1
	FOXP2	ENST00000703616.1		c.-10-51983T>C		intron	N/A	ENSP00000515400.1
	FOXP2	ENST00000960356.1		c.-10-51983T>C		intron	N/A	ENSP00000630415.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54931 AN: 151910 Hom.: 10534 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.362 AC: 54977 AN: 152028 Hom.: 10548 Cov.: 32 AF XY: 0.353 AC XY: 26240 AN XY: 74318

African (AFR) AF: 0.433 AC: 17963 AN: 41444

American (AMR) AF: 0.299 AC: 4561 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 826 AN: 3462

East Asian (EAS) AF: 0.0519 AC: 269 AN: 5180

South Asian (SAS) AF: 0.236 AC: 1140 AN: 4824

European-Finnish (FIN) AF: 0.347 AC: 3658 AN: 10554

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25482 AN: 67970

Other (OTH) AF: 0.343 AC: 723 AN: 2110

Alfa AF: 0.360 Hom.: 42702

Bravo AF: 0.363

Asia WGS AF: 0.188 AC: 655 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.79
PhyloP100		-0.0070
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: rs10249531; hg19: chr7-114014574;