rs6779258

Variant names:

• chr3-71500488-T-C
• rs6779258
• NM_001349338.3:c.-297-6933A>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.-297-6933A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,000 control chromosomes in the GnomAD database, including 9,854 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 0.34 (9854 hom., cov: 31)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-297-6933A>G		intron_variant	Intron 2 of 20	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-297-6933A>G		intron_variant	Intron 2 of 20		NM_001349338.3	ENSP00000497369.1
ENSG00000285708	ENST00000647725.1	c.-419-6933A>G		intron_variant	Intron 6 of 25			ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52276 AN: 151886 Hom.: 9852 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.344 AC: 52282 AN: 152000 Hom.: 9854 Cov.: 31 AF XY: 0.335 AC XY: 24907 AN XY: 74300

African (AFR) AF: 0.262 AC: 10869 AN: 41464

American (AMR) AF: 0.300 AC: 4586 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5168

South Asian (SAS) AF: 0.177 AC: 854 AN: 4814

European-Finnish (FIN) AF: 0.399 AC: 4213 AN: 10546

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29040 AN: 67950

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.389 Hom.: 8671

Bravo AF: 0.333

Asia WGS AF: 0.0990 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		-0.16
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: rs6779258; hg19: chr3-71549639;