rs17008402

Positions:

• chr3-71251416-A-G
• chr3-71251416-A-T

Variant summary

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

The NM_001349338.3(FOXP1):​c.-12+48404T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,170 control chromosomes in the GnomAD database, including 9,429 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 0.35 (9429 hom., cov: 33)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-12+48404T>C		intron_variant		ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-12+48404T>C		intron_variant			NM_001349338.3	ENSP00000497369	P4

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52596 AN: 152052 Hom.: 9434 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.346 AC: 52598 AN: 152170 Hom.: 9429 Cov.: 33 AF XY: 0.354 AC XY: 26329 AN XY: 74366

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.306

Alfa AF: 0.332 Hom.: 8289

Bravo AF: 0.338

Asia WGS AF: 0.520 AC: 1810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.38

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: rs17008402; hg19: chr3-71300567;