rs7616330

Positions:

• chr3-71066600-C-A
• chr3-71066600-C-T

Variant summary

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

The NM_001349338.3(FOXP1):​c.283-12827G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,118 control chromosomes in the GnomAD database, including 3,448 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 0.19 (3448 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.283-12827G>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.283-12827G>T		intron_variant			NM_001349338.3	ENSP00000497369	P4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29411 AN: 152000 Hom.: 3441 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.194 AC: 29449 AN: 152118 Hom.: 3448 Cov.: 32 AF XY: 0.202 AC XY: 15018 AN XY: 74374

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.183

Alfa AF: 0.119 Hom.: 245

Bravo AF: 0.186

Asia WGS AF: 0.491 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.81

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: rs7616330; hg19: chr3-71115751;