rs7799109

Variant names:

• chr7-114559230-T-C
• rs7799109
• NM_014491.4:c.258+24524T>C

Variant summary

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

The NM_014491.4(FOXP2):​c.258+24524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,092 control chromosomes in the GnomAD database, including 4,064 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 0.20 (4064 hom., cov: 32)
• Consequence: FOXP2 NM_014491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014491.4. 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	NM_014491.4	MANE Select	c.258+24524T>C		intron	N/A	NP_055306.1
	FOXP2	NM_148898.4		c.259-11577T>C		intron	N/A	NP_683696.2
	FOXP2	NM_148900.4		c.258+24524T>C		intron	N/A	NP_683698.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000350908.9	TSL:1 MANE Select	c.258+24524T>C		intron	N/A	ENSP00000265436.7
	FOXP2	ENST00000408937.7	TSL:1	c.259-11577T>C		intron	N/A	ENSP00000386200.3
	FOXP2	ENST00000390668.3	TSL:1	c.256-11577T>C		intron	N/A	ENSP00000375084.3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30363 AN: 151974 Hom.: 4037 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.200 AC: 30433 AN: 152092 Hom.: 4064 Cov.: 32 AF XY: 0.200 AC XY: 14854 AN XY: 74356

African (AFR) AF: 0.383 AC: 15864 AN: 41426

American (AMR) AF: 0.139 AC: 2127 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3468

East Asian (EAS) AF: 0.155 AC: 803 AN: 5164

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4828

European-Finnish (FIN) AF: 0.129 AC: 1369 AN: 10602

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7849 AN: 68000

Other (OTH) AF: 0.179 AC: 377 AN: 2112

Alfa AF: 0.144 Hom.: 1206

Bravo AF: 0.210

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7799109; hg19: chr7-114199285;