rs10511017

Positions:

• chr3-71360861-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001349338.3(FOXP1):​c.-167-1617A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,198 control chromosomes in the GnomAD database, including 2,139 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 0.16 (2139 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990

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]

ENSG00000285708 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-167-1617A>G		intron_variant		ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-167-1617A>G		intron_variant			NM_001349338.3	ENSP00000497369.1
ENSG00000285708	ENST00000647725.1	c.-289-1617A>G		intron_variant				ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24300 AN: 152078 Hom.: 2135 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.160 AC: 24314 AN: 152196 Hom.: 2139 Cov.: 32 AF XY: 0.157 AC XY: 11698 AN XY: 74408

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.155

Alfa AF: 0.189 Hom.: 3739

Bravo AF: 0.155

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	-0.22
CADD	Benign	16
DANN	Benign	0.85

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: rs10511017; hg19: chr3-71410012;