Variant 7-114570759-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000350908.9(FOXP2):c.258+36053T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,411,456 control chromosomes in the GnomAD database, including 218,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19284 hom., cov: 32)

Exomes 𝑓: 0.56 ( 198739 hom. )

Consequence

FOXP2
ENST00000350908.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.853

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-114570759-T-C is Benign according to our data. Variant chr7-114570759-T-C is described in ClinVar as [Benign]. Clinvar id is 1231050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP2	NM_014491.4 linkuse as main transcript	c.258+36053T>C		intron_variant		ENST00000350908.9	NP_055306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000350908.9 linkuse as main transcript	c.258+36053T>C		intron_variant		1	NM_014491.4	ENSP00000265436	P1	O15409-1

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74259

AN:

151506

Hom.:

19277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.534

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.747

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.541

Gnomad OTH

AF:

0.476

GnomAD3 exomes

AF:

0.560

AC:

138812

AN:

247724

Hom.:

40396

AF XY:

0.558

AC XY:

75090

AN XY:

134472

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.678

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.730

Gnomad SAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.539

Gnomad OTH exome

AF:

0.527

GnomAD4 exome

AF:

0.557

AC:

701188

AN:

1259832

Hom.:

198739

Cov.:

AF XY:

0.556

AC XY:

354464

AN XY:

637650

show subpopulations

Gnomad4 AFR exome

AF:

0.309

Gnomad4 AMR exome

AF:

0.668

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.742

Gnomad4 SAS exome

AF:

0.603

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.554

Gnomad4 OTH exome

AF:

0.545

GnomAD4 genome

AF:

0.490

AC:

74291

AN:

151624

Hom.:

19284

Cov.:

AF XY:

0.494

AC XY:

36634

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.323

Gnomad4 AMR

AF:

0.590

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.746

Gnomad4 SAS

AF:

0.604

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.506

Hom.:

9205

Bravo

AF:

0.485

Asia WGS

AF:

0.646

AC:

2247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.2

DANN

Benign

0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over