rs17137004

Variant names:

• chr7-114389196-A-G
• rs17137004
• ENST00000440349.5:n.-10-37306A>G

Variant summary

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

The ENST00000440349.5(FOXP2):​n.-10-37306A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,142 control chromosomes in the GnomAD database, including 10,857 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 0.37 (10857 hom., cov: 32)
• Consequence: FOXP2 ENST00000440349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP2	NR_033766.2	n.377-37306A>G		intron_variant	Intron 2 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000440349.5	n.-10-37306A>G		intron_variant	Intron 3 of 11	1		ENSP00000395552.1
FOXP2	ENST00000703616.1	c.-10-37306A>G		intron_variant	Intron 3 of 20			ENSP00000515400.1
FOXP2	ENST00000703613.1	c.-10-37306A>G		intron_variant	Intron 4 of 20			ENSP00000515397.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55868 AN: 152024 Hom.: 10858 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0525

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.367 AC: 55894 AN: 152142 Hom.: 10857 Cov.: 32 AF XY: 0.359 AC XY: 26676 AN XY: 74380

African (AFR) AF: 0.456 AC: 18931 AN: 41504

American (AMR) AF: 0.301 AC: 4607 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3472

East Asian (EAS) AF: 0.0519 AC: 269 AN: 5186

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3661 AN: 10584

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

European-Non Finnish (NFE) AF: 0.373 AC: 25385 AN: 67970

Other (OTH) AF: 0.349 AC: 736 AN: 2106

Alfa AF: 0.366 Hom.: 6695

Bravo AF: 0.370

Asia WGS AF: 0.183 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.060
DANN	Benign	0.56
PhyloP100		-1.9
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: rs17137004; hg19: chr7-114029251;