NM_014491.4:c.168+7523C>T

Variant names:

• chr7-114434202-C-T
• rs10268637
• NM_014491.4:c.168+7523C>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.168+7523C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,462 control chromosomes in the GnomAD database, including 19,330 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 0.50 (19330 hom., cov: 31)
• Consequence: FOXP2 NM_014491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 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.168+7523C>T		intron	N/A	NP_055306.1
	FOXP2	NM_148898.4		c.168+7523C>T		intron	N/A	NP_683696.2
	FOXP2	NM_148900.4		c.168+7523C>T		intron	N/A	NP_683698.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000350908.9	TSL:1 MANE Select	c.168+7523C>T		intron	N/A	ENSP00000265436.7
	FOXP2	ENST00000408937.7	TSL:1	c.168+7523C>T		intron	N/A	ENSP00000386200.3
	FOXP2	ENST00000390668.3	TSL:1	c.165+7523C>T		intron	N/A	ENSP00000375084.3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75079 AN: 151346 Hom.: 19308 Cov.: 31

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.496 AC: 75152 AN: 151462 Hom.: 19330 Cov.: 31 AF XY: 0.491 AC XY: 36323 AN XY: 73932

African (AFR) AF: 0.619 AC: 25612 AN: 41386

American (AMR) AF: 0.526 AC: 7997 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1180 AN: 3464

East Asian (EAS) AF: 0.371 AC: 1909 AN: 5146

South Asian (SAS) AF: 0.446 AC: 2145 AN: 4812

European-Finnish (FIN) AF: 0.394 AC: 4125 AN: 10472

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30693 AN: 67674

Other (OTH) AF: 0.470 AC: 987 AN: 2102

Alfa AF: 0.456 Hom.: 18329

Bravo AF: 0.509

Asia WGS AF: 0.426 AC: 1472 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.17
PhyloP100		-1.1
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: rs10268637; hg19: chr7-114074257;