3-70955570-G-GT

Position:

• chr3-70955570-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001349338.3(FOXP1):​c.*3676_*3677insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 197,416 control chromosomes in the GnomAD database, including 2,749 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2717 hom., cov: 30)
  • Exomes 𝑓: 0.40 (32 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 3-70955570-G-GT is Benign according to our data. Variant chr3-70955570-G-GT is described in ClinVar as [Benign]. Clinvar id is 346554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3676_*3677insA		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.*3676_*3677insA		3_prime_UTR_variant	21/21		NM_001349338.3	ENSP00000497369	P4
FOXP1	ENST00000318789.11	c.*3676_*3677insA		3_prime_UTR_variant	21/21	1		ENSP00000318902	P4

Frequencies

GnomAD3 genomes AF: 0.140 AC: 20204 AN: 144272 Hom.: 2713 Cov.: 30

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.0101

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.0497

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0832

Gnomad MID AF: 0.0676

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.403 AC: 21373 AN: 53098 Hom.: 32 Cov.: 0 AF XY: 0.402 AC XY: 9782 AN XY: 24332

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.140 AC: 20230 AN: 144318 Hom.: 2717 Cov.: 30 AF XY: 0.144 AC XY: 10090 AN XY: 70170

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.0973

Gnomad4 ASJ AF: 0.0497

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0832

Gnomad4 NFE AF: 0.0315

Gnomad4 OTH AF: 0.125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual Disability with Language Impairment and Autistic Features Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;