rs17108

chr3-71477054-G-A

Variant summary

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

The NM_001349338.3(FOXP1):c.-168+16372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,942 control chromosomes in the GnomAD database, including 10,165 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 0.36 (10165 hom., cov: 31)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP1	NM_001349338.3	c.-168+16372C>T		intron_variant		ENST00000649528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP1	ENST00000649528.3	c.-168+16372C>T		intron_variant			NM_001349338.3	P4

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54291 AN: 151824 Hom.: 10154 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.00598

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.358 AC: 54323 AN: 151942 Hom.: 10165 Cov.: 31 AF XY: 0.353 AC XY: 26183 AN XY: 74254

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.00600

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.358

Alfa AF: 0.378 Hom.: 2589

Bravo AF: 0.346

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.67
Dann	Benign	0.55

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: rs17108; hg19: chr3-71526205;