3-71481195-C-T

Position:

• chr3-71481195-C-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+12231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,050 control chromosomes in the GnomAD database, including 10,440 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 (10440 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP1	NM_001349338.3	c.-168+12231G>A		intron_variant		ENST00000649528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP1	ENST00000649528.3	c.-168+12231G>A		intron_variant			NM_001349338.3	P4

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55027 AN: 151932 Hom.: 10429 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.362 AC: 55061 AN: 152050 Hom.: 10440 Cov.: 32 AF XY: 0.357 AC XY: 26530 AN XY: 74318

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.361

Alfa AF: 0.340 Hom.: 3846

Bravo AF: 0.352

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.54

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: rs9828629; hg19: chr3-71530346; COSMIC: COSV59521851;