rs878172

Positions:

• chr3-71573298-A-G

Variant summary

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

The NM_001349338.3(FOXP1):​c.-298+8251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,420 control chromosomes in the GnomAD database, including 29,477 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 0.61 (29477 hom., cov: 30)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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-IT1 (HGNC:41335): (FOXP1 intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP1	NM_001349338.3	c.-298+8251T>C		intron_variant		ENST00000649528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP1	ENST00000649528.3	c.-298+8251T>C		intron_variant			NM_001349338.3	P4
FOXP1-IT1	ENST00000498714.1	n.963+197T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92129 AN: 151302 Hom.: 29450 Cov.: 30

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.612

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.609 AC: 92197 AN: 151420 Hom.: 29477 Cov.: 30 AF XY: 0.600 AC XY: 44372 AN XY: 73918

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.0352

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.599

Alfa AF: 0.605 Hom.: 5462

Bravo AF: 0.595

Asia WGS AF: 0.239 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.59

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: rs878172; hg19: chr3-71622449;