3-71481195-C-T

Variant names:

• chr3-71481195-C-T
• rs9828629
• NM_001349338.3:c.-168+12231G>A

Variant summary

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

The NM_001349338.3(FOXP1):​c.-168+12231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,050 control chromosomes in the GnomAD database, including 10,440 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 0.36 (10440 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 21 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, ClinGen
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	NM_001349338.3	MANE Select	c.-168+12231G>A		intron	N/A	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.-168+12231G>A		intron	N/A	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244816.2		c.-168+12231G>A		intron	N/A	NP_001231745.1	Q9H334-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.-168+12231G>A		intron	N/A	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.-168+12231G>A		intron	N/A	ENSP00000318902.5	Q9H334-1
	ENSG00000285708	ENST00000647725.1		c.-290+12231G>A		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55027 AN: 151932 Hom.: 10429 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.362 AC: 55061 AN: 152050 Hom.: 10440 Cov.: 32 AF XY: 0.357 AC XY: 26530 AN XY: 74318

African (AFR) AF: 0.397 AC: 16467 AN: 41448

American (AMR) AF: 0.294 AC: 4495 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1403 AN: 3472

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5182

South Asian (SAS) AF: 0.280 AC: 1348 AN: 4822

European-Finnish (FIN) AF: 0.388 AC: 4095 AN: 10558

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26015 AN: 67974

Other (OTH) AF: 0.361 AC: 762 AN: 2112

Alfa AF: 0.348 Hom.: 5598

Bravo AF: 0.352

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.54
PhyloP100		-0.11
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: rs9828629; hg19: chr3-71530346; COSMIC: COSV59521851;