rs6802472

Variant names:

• chr3-70987843-A-G
• rs6802472
• NM_001349338.3:c.1146+151T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-70987843-A-G
• chr3-70987843-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001349338.3(FOXP1):​c.1146+151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 708,862 control chromosomes in the GnomAD database, including 61,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (20069 hom., cov: 33)
  • Exomes 𝑓: 0.33 (41592 hom.)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0540
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-70987843-A-G is Benign according to our data. Variant chr3-70987843-A-G is described in ClinVar as Benign. ClinVar VariationId is 1180354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 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.1146+151T>C		intron	N/A	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.1146+151T>C		intron	N/A	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244814.3		c.1146+151T>C		intron	N/A	NP_001231743.1	Q9H334-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.1146+151T>C		intron	N/A	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.1146+151T>C		intron	N/A	ENSP00000318902.5	Q9H334-1
	ENSG00000285708	ENST00000647725.1		c.1146+151T>C		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65875 AN: 152016 Hom.: 20000 Cov.: 33

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.327 AC: 182125 AN: 556728 Hom.: 41592 AF XY: 0.331 AC XY: 98907 AN XY: 298984

African (AFR) AF: 0.818 AC: 12247 AN: 14964

American (AMR) AF: 0.284 AC: 8138 AN: 28608

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 2163 AN: 15604

East Asian (EAS) AF: 0.911 AC: 32034 AN: 35162

South Asian (SAS) AF: 0.528 AC: 28662 AN: 54332

European-Finnish (FIN) AF: 0.348 AC: 16522 AN: 47440

Middle Eastern (MID) AF: 0.260 AC: 558 AN: 2146

European-Non Finnish (NFE) AF: 0.220 AC: 72161 AN: 328708

Other (OTH) AF: 0.324 AC: 9640 AN: 29764

GnomAD4 genome AF: 0.434 AC: 66004 AN: 152134 Hom.: 20069 Cov.: 33 AF XY: 0.444 AC XY: 33060 AN XY: 74386

African (AFR) AF: 0.816 AC: 33874 AN: 41494

American (AMR) AF: 0.292 AC: 4464 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4602 AN: 5168

South Asian (SAS) AF: 0.557 AC: 2688 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3881 AN: 10592

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14912 AN: 67976

Other (OTH) AF: 0.388 AC: 820 AN: 2112

Alfa AF: 0.260 Hom.: 11921

Bravo AF: 0.447

Asia WGS AF: 0.759 AC: 2636 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		-0.054
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: rs6802472; hg19: chr3-71036994;