3-71546107-T-C

Variant names:

• chr3-71546107-T-C
• rs11720121
• NM_001349338.3:c.-298+35442A>G

Variant summary

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

The NM_001349338.3(FOXP1):​c.-298+35442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,012 control chromosomes in the GnomAD database, including 8,071 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 0.30 (8071 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	NM_001349338.3	MANE Select	c.-298+35442A>G		intron	N/A	NP_001336267.1
	FOXP1	NM_001244810.2		c.-298+35442A>G		intron	N/A	NP_001231739.1
	FOXP1	NM_001349340.3		c.-203+35442A>G		intron	N/A	NP_001336269.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.-298+35442A>G		intron	N/A	ENSP00000497369.1
	FOXP1	ENST00000318789.11	TSL:1	c.-298+35442A>G		intron	N/A	ENSP00000318902.5
	ENSG00000285708	ENST00000647725.1		c.-419-52552A>G		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45473 AN: 151894 Hom.: 8073 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.299 AC: 45469 AN: 152012 Hom.: 8071 Cov.: 32 AF XY: 0.294 AC XY: 21828 AN XY: 74304

African (AFR) AF: 0.149 AC: 6199 AN: 41470

American (AMR) AF: 0.283 AC: 4331 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1510 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.170 AC: 816 AN: 4808

European-Finnish (FIN) AF: 0.386 AC: 4070 AN: 10540

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27327 AN: 67952

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.363 Hom.: 5319

Bravo AF: 0.284

Asia WGS AF: 0.0890 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		0.51
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: rs11720121; hg19: chr3-71595258;