chr3-71006011-G-A

Position:

• chr3-71006011-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.975-4952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,896 control chromosomes in the GnomAD database, including 12,886 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 0.37 (12886 hom., cov: 31)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.975-4952C>T		intron_variant		ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.975-4952C>T		intron_variant			NM_001349338.3	ENSP00000497369	P4

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55532 AN: 151776 Hom.: 12885 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.366 AC: 55527 AN: 151896 Hom.: 12886 Cov.: 31 AF XY: 0.358 AC XY: 26578 AN XY: 74230

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.0217

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.390

Alfa AF: 0.446 Hom.: 9119

Bravo AF: 0.359

Asia WGS AF: 0.128 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.92

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: rs13093086; hg19: chr3-71055162;