3-71251416-A-G

Variant names:

• chr3-71251416-A-G
• rs17008402
• NM_001349338.3:c.-12+48404T>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.-12+48404T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,170 control chromosomes in the GnomAD database, including 9,429 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 (9429 hom., cov: 33)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• 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: 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 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.-12+48404T>C		intron	N/A	NP_001336267.1
	FOXP1	NM_001244810.2		c.-12+48404T>C		intron	N/A	NP_001231739.1
	FOXP1	NM_001244816.2		c.-12+48404T>C		intron	N/A	NP_001231745.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.-12+48404T>C		intron	N/A	ENSP00000497369.1
	FOXP1	ENST00000318789.11	TSL:1	c.-12+48404T>C		intron	N/A	ENSP00000318902.5
	ENSG00000285708	ENST00000647725.1		c.-12+48404T>C		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52596 AN: 152052 Hom.: 9434 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.346 AC: 52598 AN: 152170 Hom.: 9429 Cov.: 33 AF XY: 0.354 AC XY: 26329 AN XY: 74366

African (AFR) AF: 0.311 AC: 12897 AN: 41502

American (AMR) AF: 0.389 AC: 5947 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3468

East Asian (EAS) AF: 0.599 AC: 3095 AN: 5164

South Asian (SAS) AF: 0.507 AC: 2445 AN: 4826

European-Finnish (FIN) AF: 0.390 AC: 4124 AN: 10582

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22320 AN: 68014

Other (OTH) AF: 0.306 AC: 646 AN: 2114

Alfa AF: 0.337 Hom.: 26740

Bravo AF: 0.338

Asia WGS AF: 0.520 AC: 1810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.38
PhyloP100		-0.37
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: rs17008402; hg19: chr3-71300567;