rs11720523

Variant names:

• chr3-71496019-C-A
• rs11720523
• NM_001349338.3:c.-297-2464G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349338.3(FOXP1):​c.-297-2464G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,052 control chromosomes in the GnomAD database, including 9,962 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 0.35 (9962 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 15 publications found

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]

FOXP1 Gene-Disease associations (from GenCC):

• intellectual disability-severe speech delay-mild dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000285708 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-297-2464G>T		intron_variant	Intron 2 of 20	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-297-2464G>T		intron_variant	Intron 2 of 20		NM_001349338.3	ENSP00000497369.1
ENSG00000285708	ENST00000647725.1	c.-419-2464G>T		intron_variant	Intron 6 of 25			ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52855 AN: 151934 Hom.: 9961 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.348 AC: 52861 AN: 152052 Hom.: 9962 Cov.: 32 AF XY: 0.339 AC XY: 25181 AN XY: 74290

African (AFR) AF: 0.284 AC: 11774 AN: 41448

American (AMR) AF: 0.299 AC: 4565 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5190

South Asian (SAS) AF: 0.178 AC: 859 AN: 4820

European-Finnish (FIN) AF: 0.400 AC: 4221 AN: 10542

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28838 AN: 67988

Other (OTH) AF: 0.369 AC: 776 AN: 2104

Alfa AF: 0.391 Hom.: 6299

Bravo AF: 0.337

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.46
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11720523; hg19: chr3-71545170;