chr3-70955832-G-GCACACACA

Position:

• chr3-70955832-G-GCACACACA

Variant summary

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

The NM_001349338.3(FOXP1):​c.*3414_*3415insTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 221,220 control chromosomes in the GnomAD database, including 126 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.024 (126 hom., cov: 26)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.373

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 (EAS) allele frequency at 95% confidence interval = 0.0709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP1	NM_001349338.3	c.*3414_*3415insTGTGTGTG		3_prime_UTR_variant	21/21	ENST00000649528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP1	ENST00000649528.3	c.*3414_*3415insTGTGTGTG		3_prime_UTR_variant	21/21		NM_001349338.3	P4
FOXP1	ENST00000318789.11	c.*3414_*3415insTGTGTGTG		3_prime_UTR_variant	21/21	1		P4

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3594 AN: 147114 Hom.: 126 Cov.: 26

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00813

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.000314

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000814

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.0136 AC: 1003 AN: 74010 Hom.: 0 Cov.: 0 AF XY: 0.0126 AC XY: 429 AN XY: 34000

Gnomad4 AFR exome AF: 0.0764

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00173

Gnomad4 EAS exome AF: 0.0512

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.00633

Gnomad4 NFE exome AF: 0.000935

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.0245 AC: 3601 AN: 147210 Hom.: 126 Cov.: 26 AF XY: 0.0242 AC XY: 1735 AN XY: 71594

Gnomad4 AFR AF: 0.0731

Gnomad4 AMR AF: 0.00812

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.0754

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.000314

Gnomad4 NFE AF: 0.000814

Gnomad4 OTH AF: 0.0147

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual Disability with Language Impairment and Autistic Features Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143202281; hg19: chr3-71004983;