rs7639736

Positions:

• chr3-70959406-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001349338.3(FOXP1):​c.1890-15G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,613,826 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (133 hom., cov: 31)
  • Exomes 𝑓: 0.015 (460 hom.)
• Consequence: FOXP1 NM_001349338.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.151

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-70959406-C-A is Benign according to our data. Variant chr3-70959406-C-A is described in ClinVar as [Benign]. Clinvar id is 1282214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.1890-15G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.1890-15G>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001349338.3	ENSP00000497369	P4

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5190 AN: 151996 Hom.: 132 Cov.: 31

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00831

Gnomad OTH AF: 0.0254

GnomAD3 exomes AF: 0.0285 AC: 7157 AN: 250992 Hom.: 221 AF XY: 0.0258 AC XY: 3495 AN XY: 135656

Gnomad AFR exome AF: 0.0727

Gnomad AMR exome AF: 0.0631

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.0720

Gnomad SAS exome AF: 0.0217

Gnomad FIN exome AF: 0.0331

Gnomad NFE exome AF: 0.00782

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.0147 AC: 21492 AN: 1461712 Hom.: 460 Cov.: 34 AF XY: 0.0146 AC XY: 10594 AN XY: 727148

Gnomad4 AFR exome AF: 0.0692

Gnomad4 AMR exome AF: 0.0622

Gnomad4 ASJ exome AF: 0.00551

Gnomad4 EAS exome AF: 0.0835

Gnomad4 SAS exome AF: 0.0210

Gnomad4 FIN exome AF: 0.0318

Gnomad4 NFE exome AF: 0.00741

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0342 AC: 5202 AN: 152114 Hom.: 133 Cov.: 31 AF XY: 0.0350 AC XY: 2604 AN XY: 74346

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.0520

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.0812

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0323

Gnomad4 NFE AF: 0.00831

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0219 Hom.: 23

Bravo AF: 0.0381

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.39

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: rs7639736; hg19: chr3-71008557;