3-71120841-T-G

Variant names:

• chr3-71120841-T-G
• rs831451
• NM_001349338.3:c.181-8204A>C

Variant summary

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

The NM_001349338.3(FOXP1):​c.181-8204A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,976 control chromosomes in the GnomAD database, including 7,773 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 0.31 (7773 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 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.181-8204A>C		intron	N/A	NP_001336267.1
	FOXP1	NM_001244810.2		c.181-8204A>C		intron	N/A	NP_001231739.1
	FOXP1	NM_001244814.3		c.181-8204A>C		intron	N/A	NP_001231743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.181-8204A>C		intron	N/A	ENSP00000497369.1
	FOXP1	ENST00000318789.11	TSL:1	c.181-8204A>C		intron	N/A	ENSP00000318902.5
	ENSG00000285708	ENST00000647725.1		c.181-8204A>C		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46877 AN: 151858 Hom.: 7769 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.309 AC: 46890 AN: 151976 Hom.: 7773 Cov.: 32 AF XY: 0.313 AC XY: 23241 AN XY: 74290

African (AFR) AF: 0.219 AC: 9061 AN: 41460

American (AMR) AF: 0.303 AC: 4620 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3111 AN: 5152

South Asian (SAS) AF: 0.489 AC: 2359 AN: 4820

European-Finnish (FIN) AF: 0.301 AC: 3177 AN: 10554

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22547 AN: 67944

Other (OTH) AF: 0.309 AC: 650 AN: 2106

Alfa AF: 0.184 Hom.: 364

Bravo AF: 0.301

Asia WGS AF: 0.548 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.63
PhyloP100		0.037
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: rs831451; hg19: chr3-71169992;