rs7787510

Variant names:

• chr7-114651381-T-C
• rs7787510
• NM_014491.4:c.1095-822T>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.1095-822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,134 control chromosomes in the GnomAD database, including 1,569 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 0.10 (1569 hom., cov: 32)
• Consequence: FOXP2 NM_014491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 1 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)

ENSG00000303050 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 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.1095-822T>C		intron	N/A	NP_055306.1
	FOXP2	NM_148898.4		c.1170-822T>C		intron	N/A	NP_683696.2
	FOXP2	NM_148900.4		c.1146-822T>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.1095-822T>C		intron	N/A	ENSP00000265436.7
	FOXP2	ENST00000408937.7	TSL:1	c.1170-822T>C		intron	N/A	ENSP00000386200.3
	FOXP2	ENST00000390668.3	TSL:1	c.1167-822T>C		intron	N/A	ENSP00000375084.3

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15216 AN: 152016 Hom.: 1575 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.0760

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.00914

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.100 AC: 15227 AN: 152134 Hom.: 1569 Cov.: 32 AF XY: 0.0973 AC XY: 7234 AN XY: 74370

African (AFR) AF: 0.267 AC: 11090 AN: 41496

American (AMR) AF: 0.0659 AC: 1005 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0760 AC: 264 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00891 AC: 43 AN: 4828

European-Finnish (FIN) AF: 0.00914 AC: 97 AN: 10612

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0359 AC: 2437 AN: 67968

Other (OTH) AF: 0.109 AC: 230 AN: 2114

Alfa AF: 0.0729 Hom.: 131

Bravo AF: 0.111

Asia WGS AF: 0.0190 AC: 64 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.85
PhyloP100		-0.10
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: rs7787510; hg19: chr7-114291436;