rs17651978

chr3-70971339-G-Achr3-70971339-G-C

Variant summary

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

The NM_001349338.3(FOXP1):c.1653-534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 166,052 control chromosomes in the GnomAD database, including 3,417 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 0.17 (3102 hom., cov: 32)
  • Exomes 𝑓: 0.18 (315 hom.)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP1	NM_001349338.3	c.1653-534C>T		intron_variant		ENST00000649528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP1	ENST00000649528.3	c.1653-534C>T		intron_variant			NM_001349338.3	P4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26517 AN: 152042 Hom.: 3104 Cov.: 32

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.182 AC: 2531 AN: 13892 Hom.: 315 Cov.: 0 AF XY: 0.179 AC XY: 1272 AN XY: 7114

Gnomad4 AFR exome AF: 0.0341

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.174 AC: 26509 AN: 152160 Hom.: 3102 Cov.: 32 AF XY: 0.170 AC XY: 12631 AN XY: 74380

Gnomad4 AFR AF: 0.0439

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.179

Alfa AF: 0.227 Hom.: 4335

Bravo AF: 0.164

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.78
Dann	Benign	0.52

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: rs17651978; hg19: chr3-71020490;