7-114103777-A-T

Variant names:

• chr7-114103777-A-T
• rs7785744
• ENST00000440349.5:n.-247+17166A>T

Variant summary

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

The ENST00000440349.5(FOXP2):​n.-247+17166A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,660 control chromosomes in the GnomAD database, including 17,587 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 0.47 (17587 hom., cov: 32)
• Consequence: FOXP2 ENST00000440349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 2 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 = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000440349.5. 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	NR_033766.2		n.285+17166A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000440349.5	TSL:1	n.-247+17166A>T		intron	N/A	ENSP00000395552.1
	FOXP2	ENST00000703616.1		c.-247+15939A>T		intron	N/A	ENSP00000515400.1
	FOXP2	ENST00000703613.1		c.-365+17166A>T		intron	N/A	ENSP00000515397.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70838 AN: 151542 Hom.: 17560 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.468 AC: 70916 AN: 151660 Hom.: 17587 Cov.: 32 AF XY: 0.468 AC XY: 34680 AN XY: 74110

African (AFR) AF: 0.634 AC: 26249 AN: 41396

American (AMR) AF: 0.388 AC: 5904 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2622 AN: 5154

South Asian (SAS) AF: 0.391 AC: 1883 AN: 4818

European-Finnish (FIN) AF: 0.368 AC: 3867 AN: 10518

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.405 AC: 27436 AN: 67790

Other (OTH) AF: 0.459 AC: 965 AN: 2104

Alfa AF: 0.221 Hom.: 478

Bravo AF: 0.472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.36
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7785744; hg19: chr7-113743832;