rs1229761

Variant names:

• chr7-114583668-C-A
• rs1229761
• NM_014491.4:c.259-44872C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-114583668-C-A
• chr7-114583668-C-G
• chr7-114583668-C-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.259-44872C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,122 control chromosomes in the GnomAD database, including 41,386 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 0.73 (41386 hom., cov: 33)
• Consequence: FOXP2 NM_014491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 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.259-44872C>A		intron	N/A	NP_055306.1	O15409-1
	FOXP2	NM_148898.4		c.333+12787C>A		intron	N/A	NP_683696.2	O15409-4
	FOXP2	NM_148900.4		c.259-44872C>A		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.259-44872C>A		intron	N/A	ENSP00000265436.7	O15409-1
	FOXP2	ENST00000408937.7	TSL:1	c.333+12787C>A		intron	N/A	ENSP00000386200.3	O15409-4
	FOXP2	ENST00000390668.3	TSL:1	c.330+12787C>A		intron	N/A	ENSP00000375084.3	Q8N6B5

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110988 AN: 152004 Hom.: 41329 Cov.: 33

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.730 AC: 111107 AN: 152122 Hom.: 41386 Cov.: 33 AF XY: 0.734 AC XY: 54571 AN XY: 74352

African (AFR) AF: 0.836 AC: 34704 AN: 41530

American (AMR) AF: 0.755 AC: 11544 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2064 AN: 3472

East Asian (EAS) AF: 0.980 AC: 5073 AN: 5176

South Asian (SAS) AF: 0.854 AC: 4121 AN: 4828

European-Finnish (FIN) AF: 0.661 AC: 6979 AN: 10556

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44442 AN: 67958

Other (OTH) AF: 0.695 AC: 1463 AN: 2106

Alfa AF: 0.667 Hom.: 59216

Bravo AF: 0.741

Asia WGS AF: 0.889 AC: 3092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.39
PhyloP100		0.51
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: rs1229761; hg19: chr7-114223723;