rs17651978

Variant names:

• chr3-70971339-G-A
• rs17651978
• NM_001349338.3:c.1653-534C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-70971339-G-A
• chr3-70971339-G-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.1653-534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 166,052 control chromosomes in the GnomAD database, including 3,417 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 0.17 (3102 hom., cov: 32)
  • Exomes 𝑓: 0.18 (315 hom.)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 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.1653-534C>T		intron	N/A	NP_001336267.1
	FOXP1	NM_001244810.2		c.1701-534C>T		intron	N/A	NP_001231739.1
	FOXP1	NM_001244814.3		c.1653-534C>T		intron	N/A	NP_001231743.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.1653-534C>T		intron	N/A	ENSP00000497369.1
	FOXP1	ENST00000318789.11	TSL:1	c.1653-534C>T		intron	N/A	ENSP00000318902.5
	ENSG00000285708	ENST00000647725.1		c.1653-534C>T		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26517 AN: 152042 Hom.: 3104 Cov.: 32

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.182 AC: 2531 AN: 13892 Hom.: 315 Cov.: 0 AF XY: 0.179 AC XY: 1272 AN XY: 7114

African (AFR) AF: 0.0341 AC: 6 AN: 176

American (AMR) AF: 0.135 AC: 329 AN: 2438

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 36 AN: 152

East Asian (EAS) AF: 0.00 AC: 0 AN: 754

South Asian (SAS) AF: 0.125 AC: 197 AN: 1570

European-Finnish (FIN) AF: 0.158 AC: 46 AN: 292

Middle Eastern (MID) AF: 0.292 AC: 7 AN: 24

European-Non Finnish (NFE) AF: 0.226 AC: 1773 AN: 7844

Other (OTH) AF: 0.213 AC: 137 AN: 642

GnomAD4 genome AF: 0.174 AC: 26509 AN: 152160 Hom.: 3102 Cov.: 32 AF XY: 0.170 AC XY: 12631 AN XY: 74380

African (AFR) AF: 0.0439 AC: 1823 AN: 41522

American (AMR) AF: 0.160 AC: 2446 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.133 AC: 642 AN: 4826

European-Finnish (FIN) AF: 0.209 AC: 2213 AN: 10586

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17660 AN: 67982

Other (OTH) AF: 0.179 AC: 377 AN: 2106

Alfa AF: 0.212 Hom.: 6692

Bravo AF: 0.164

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.52
PhyloP100		-2.2
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: rs17651978; hg19: chr3-71020490;