3-70955832-G-GCA

Position:

• chr3-70955832-G-GCA

Variant summary

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

The NM_001349338.3(FOXP1):​c.*3414_*3415insTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 221,286 control chromosomes in the GnomAD database, including 176 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (174 hom., cov: 26)
  • Exomes 𝑓: 0.044 (2 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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 (NFE) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3414_*3415insTG		3_prime_UTR_variant	21/21	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.*3414_*3415insTG		3_prime_UTR_variant	21/21		NM_001349338.3	ENSP00000497369	P4
FOXP1	ENST00000318789.11	c.*3414_*3415insTG		3_prime_UTR_variant	21/21	1		ENSP00000318902	P4

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7088 AN: 147110 Hom.: 175 Cov.: 26

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.0168

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.00796

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0438 AC: 3245 AN: 74082 Hom.: 2 Cov.: 0 AF XY: 0.0430 AC XY: 1463 AN XY: 34058

Gnomad4 AFR exome AF: 0.0469

Gnomad4 AMR exome AF: 0.0355

Gnomad4 ASJ exome AF: 0.0317

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.0379

Gnomad4 FIN exome AF: 0.0316

Gnomad4 NFE exome AF: 0.0536

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0482 AC: 7090 AN: 147204 Hom.: 174 Cov.: 26 AF XY: 0.0480 AC XY: 3434 AN XY: 71588

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.00797

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0786

Gnomad4 NFE AF: 0.0556

Gnomad4 OTH AF: 0.0420

Bravo AF: 0.0438

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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;