Variant 3-70965870-G-T 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 NM_001349338.3(FOXP1):c.1889+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,612,816 control chromosomes in the GnomAD database, including 694,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68269 hom., cov: 30)

Exomes 𝑓: 0.93 ( 625832 hom. )

Consequence

FOXP1
NM_001349338.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

FOXP1 (HGNC:3823): (forkhead box P1) This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FOXP1 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=-0.91).

BP6

Variant 3-70965870-G-T is Benign according to our data. Variant chr3-70965870-G-T is described in ClinVar as [Benign]. Clinvar id is 96228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-70965870-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3 linkuse as main transcript	c.1889+20C>A		intron_variant		ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3 linkuse as main transcript	c.1889+20C>A		intron_variant			NM_001349338.3	ENSP00000497369	P4	Q9H334-1

Frequencies

GnomAD3 genomes

AF:

0.947

AC:

143909

AN:

152028

Hom.:

68210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.984

Gnomad AMI

AF:

0.919

Gnomad AMR

AF:

0.943

Gnomad ASJ

AF:

0.914

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.975

Gnomad FIN

AF:

0.948

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.920

Gnomad OTH

AF:

0.943

GnomAD3 exomes

AF:

0.945

AC:

237666

AN:

251442

Hom.:

112437

AF XY:

0.944

AC XY:

128324

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.987

Gnomad AMR exome

AF:

0.963

Gnomad ASJ exome

AF:

0.915

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.972

Gnomad FIN exome

AF:

0.944

Gnomad NFE exome

AF:

0.921

Gnomad OTH exome

AF:

0.940

GnomAD4 exome

AF:

0.925

AC:

1351559

AN:

1460670

Hom.:

625832

Cov.:

AF XY:

0.927

AC XY:

673551

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.987

Gnomad4 AMR exome

AF:

0.963

Gnomad4 ASJ exome

AF:

0.915

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.972

Gnomad4 FIN exome

AF:

0.946

Gnomad4 NFE exome

AF:

0.915

Gnomad4 OTH exome

AF:

0.926

GnomAD4 genome

AF:

0.947

AC:

144027

AN:

152146

Hom.:

68269

Cov.:

AF XY:

0.949

AC XY:

70578

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.985

Gnomad4 AMR

AF:

0.943

Gnomad4 ASJ

AF:

0.914

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.974

Gnomad4 FIN

AF:

0.948

Gnomad4 NFE

AF:

0.920

Gnomad4 OTH

AF:

0.944

Alfa

AF:

0.935

Hom.:

13650

Bravo

AF:

0.948

Asia WGS

AF:

0.987

AC:

3428

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 16, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 20, 2017	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Intellectual disability-severe speech delay-mild dysmorphism syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.015

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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