chr7-114213034-T-C

Position:

• chr7-114213034-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000703616.1(FOXP2):​c.-102+49946T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,162 control chromosomes in the GnomAD database, including 5,273 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 0.25 (5273 hom., cov: 32)
• Consequence: FOXP2 ENST00000703616.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP2	NR_033766.2	n.286-74985T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000440349.5	n.-102+49946T>C		intron_variant		1		ENSP00000395552.1
FOXP2	ENST00000703616.1	c.-102+49946T>C		intron_variant				ENSP00000515400.1
FOXP2	ENST00000703613.1	c.-102+49946T>C		intron_variant				ENSP00000515397.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37661 AN: 152044 Hom.: 5259 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0344

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.248 AC: 37713 AN: 152162 Hom.: 5273 Cov.: 32 AF XY: 0.241 AC XY: 17935 AN XY: 74398

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0339

Gnomad4 SAS AF: 0.0748

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.229

Alfa AF: 0.234 Hom.: 8465

Bravo AF: 0.247

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs717233; hg19: chr7-113853089;