3-70955832-G-GCGCACA

Position:

• chr3-70955832-G-GCGCACA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001349338.3(FOXP1):​c.*3414_*3415insTGTGCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 221,612 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (5 hom., cov: 26)
  • Exomes 𝑓: 0.00090 (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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00452 (666/147254) while in subpopulation AFR AF= 0.0152 (616/40398). AF 95% confidence interval is 0.0143. There are 5 homozygotes in gnomad4. There are 322 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 666 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 662 AN: 147158 Hom.: 5 Cov.: 26

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00260

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000753

Gnomad OTH AF: 0.00346

GnomAD4 exome AF: 0.000901 AC: 67 AN: 74358 Hom.: 0 Cov.: 0 AF XY: 0.000761 AC XY: 26 AN XY: 34160

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000222

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00452 AC: 666 AN: 147254 Hom.: 5 Cov.: 26 AF XY: 0.00450 AC XY: 322 AN XY: 71612

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.00259

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000753

Gnomad4 OTH AF: 0.00342

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: rs1553648184; hg19: chr3-71004983;