3-71489545-G-T

Position:

• chr3-71489545-G-T

Variant summary

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

The NM_001349338.3(FOXP1):​c.-168+3881C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,124 control chromosomes in the GnomAD database, including 6,383 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 0.28 (6383 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-168+3881C>A		intron_variant		ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-168+3881C>A		intron_variant			NM_001349338.3	ENSP00000497369	P4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42822 AN: 152006 Hom.: 6382 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.282 AC: 42833 AN: 152124 Hom.: 6383 Cov.: 32 AF XY: 0.274 AC XY: 20387 AN XY: 74354

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.307

Alfa AF: 0.306 Hom.: 3397

Bravo AF: 0.276

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.9
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: rs6549392; hg19: chr3-71538696;