rs2121783

Positions:

• chr3-71125324-C-T

Variant summary

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

The NM_001349338.3(FOXP1):​c.181-12687G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,050 control chromosomes in the GnomAD database, including 20,669 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 0.51 (20669 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP1	NM_001349338.3	c.181-12687G>A		intron_variant		ENST00000649528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP1	ENST00000649528.3	c.181-12687G>A		intron_variant			NM_001349338.3	P4

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77786 AN: 151932 Hom.: 20656 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.512 AC: 77837 AN: 152050 Hom.: 20669 Cov.: 32 AF XY: 0.508 AC XY: 37755 AN XY: 74312

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.551

Alfa AF: 0.575 Hom.: 36739

Bravo AF: 0.509

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0050
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs2121783; hg19: chr3-71174475;