rs1901186

Variant names:

• chr7-114117121-C-T
• rs1901186
• ENST00000440349.5:n.-247+30510C>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+30510C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,800 control chromosomes in the GnomAD database, including 7,921 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 0.26 (7921 hom., cov: 31)
• Consequence: FOXP2 ENST00000440349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• 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: 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP2	NR_033766.2	n.285+30510C>T		intron_variant	Intron 1 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000440349.5	n.-247+30510C>T		intron_variant	Intron 1 of 11	1		ENSP00000395552.1
FOXP2	ENST00000703616.1	c.-247+29283C>T		intron_variant	Intron 1 of 20			ENSP00000515400.1
FOXP2	ENST00000703613.1	c.-364-15264C>T		intron_variant	Intron 1 of 20			ENSP00000515397.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39259 AN: 151682 Hom.: 7897 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.259 AC: 39340 AN: 151800 Hom.: 7921 Cov.: 31 AF XY: 0.262 AC XY: 19453 AN XY: 74192

African (AFR) AF: 0.548 AC: 22680 AN: 41366

American (AMR) AF: 0.199 AC: 3032 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2543 AN: 5160

South Asian (SAS) AF: 0.254 AC: 1221 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1217 AN: 10510

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7572 AN: 67944

Other (OTH) AF: 0.234 AC: 491 AN: 2102

Alfa AF: 0.170 Hom.: 919

Bravo AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.8
DANN	Benign	0.42
PhyloP100		0.47
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: rs1901186; hg19: chr7-113757176;