3-70955638-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001349338.3(FOXP1):c.*3608_*3609insT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00389 in 233,496 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (1 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.31

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 3-70955638-T-TA is Benign according to our data. Variant chr3-70955638-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 346556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00358 (545/152194) while in subpopulation SAS AF= 0.0147 (71/4818). AF 95% confidence interval is 0.012. There are 4 homozygotes in gnomad4. There are 276 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 546 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP1	NM_001349338.3	c.*3608_*3609insT		3_prime_UTR_variant	21/21	ENST00000649528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP1	ENST00000649528.3	c.*3608_*3609insT		3_prime_UTR_variant	21/21		NM_001349338.3	P4
FOXP1	ENST00000318789.11	c.*3608_*3609insT		3_prime_UTR_variant	21/21	1		P4

Frequencies

GnomAD3 genomes AF: 0.00359 AC: 546 AN: 152076 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00515

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.00448 AC: 364 AN: 81302 Hom.: 1 Cov.: 0 AF XY: 0.00489 AC XY: 183 AN XY: 37416

Gnomad4 AFR exome AF: 0.000257

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00898

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0214

Gnomad4 FIN exome AF: 0.00881

Gnomad4 NFE exome AF: 0.00522

Gnomad4 OTH exome AF: 0.00473

GnomAD4 genome AF: 0.00358 AC: 545 AN: 152194 Hom.: 4 Cov.: 32 AF XY: 0.00371 AC XY: 276 AN XY: 74416

Gnomad4 AFR AF: 0.000723

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.00302

Gnomad4 NFE AF: 0.00515

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00432 Hom.: 0

Bravo AF: 0.00297

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual Disability with Language Impairment and Autistic Features Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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: rs533607618; hg19: chr3-71004789;