rs7788346

Variant names:

• chr7-114573188-C-T
• rs7788346
• NM_014491.4:c.258+38482C>T

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+38482C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 151,730 control chromosomes in the GnomAD database, including 1,050 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 0.081 (1050 hom., cov: 32)
• Consequence: FOXP2 NM_014491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	NM_014491.4	MANE Select	c.258+38482C>T		intron	N/A	NP_055306.1	O15409-1
	FOXP2	NM_148898.4		c.333+2307C>T		intron	N/A	NP_683696.2	O15409-4
	FOXP2	NM_148900.4		c.258+38482C>T		intron	N/A	NP_683698.2	O15409-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000350908.9	TSL:1 MANE Select	c.258+38482C>T		intron	N/A	ENSP00000265436.7	O15409-1
	FOXP2	ENST00000408937.7	TSL:1	c.333+2307C>T		intron	N/A	ENSP00000386200.3	O15409-4
	FOXP2	ENST00000390668.3	TSL:1	c.330+2307C>T		intron	N/A	ENSP00000375084.3	Q8N6B5

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12321 AN: 151612 Hom.: 1046 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0523

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0701

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

GnomAD4 genome AF: 0.0814 AC: 12351 AN: 151730 Hom.: 1050 Cov.: 32 AF XY: 0.0824 AC XY: 6108 AN XY: 74168

African (AFR) AF: 0.199 AC: 8243 AN: 41388

American (AMR) AF: 0.0615 AC: 934 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.0523 AC: 181 AN: 3462

East Asian (EAS) AF: 0.234 AC: 1206 AN: 5158

South Asian (SAS) AF: 0.116 AC: 559 AN: 4822

European-Finnish (FIN) AF: 0.0194 AC: 205 AN: 10590

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0127 AC: 859 AN: 67818

Other (OTH) AF: 0.0698 AC: 147 AN: 2106

Alfa AF: 0.0356 Hom.: 164

Bravo AF: 0.0923

Asia WGS AF: 0.166 AC: 576 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.6
DANN	Benign	0.35
PhyloP100		-0.040
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7788346;

hg19: chr7-114213243;