3-70955570-GTTTT-GTTT

Variant names:

• chr3-70955570-GT-G
• rs35502550
• NM_001349338.3:c.*3676delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001349338.3(FOXP1):​c.*3676delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 214,288 control chromosomes in the GnomAD database, including 103 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.021 (102 hom., cov: 30)
  • Exomes 𝑓: 0.022 (1 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3676delA		3_prime_UTR_variant	Exon 21 of 21	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528	c.*3676delA		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789	c.*3676delA		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3096 AN: 144600 Hom.: 102 Cov.: 30

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00931

Gnomad ASJ AF: 0.000299

Gnomad EAS AF: 0.00159

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.00168

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.0152

GnomAD4 exome AF: 0.0218 AC: 1520 AN: 69636 Hom.: 1 Cov.: 0 AF XY: 0.0209 AC XY: 670 AN XY: 32056

Gnomad4 AFR exome AF: 0.0789

Gnomad4 AMR exome AF: 0.0250

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.00425

Gnomad4 SAS exome AF: 0.0127

Gnomad4 FIN exome AF: 0.0174

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.0274

GnomAD4 genome AF: 0.0214 AC: 3101 AN: 144652 Hom.: 102 Cov.: 30 AF XY: 0.0215 AC XY: 1513 AN XY: 70344

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.00930

Gnomad4 ASJ AF: 0.000299

Gnomad4 EAS AF: 0.00159

Gnomad4 SAS AF: 0.00110

Gnomad4 FIN AF: 0.00168

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.0151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs35502550; hg19: chr3-71004721;